Materiały źródłowe

• #1 Pathology of esophageal cancer and Barrett’s esophagus – Jain- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/14047/html

  Esophageal cancer is a serious malignancy with high mortality. The two common distinctive pathologic subtypes of esophageal cancer are squamous cell carcinoma and adenocarcinoma. These differ with regards to etiology, ethnic distribution, pathogenesis, and location in the esophagus. […] Esophageal cancer represents 1% of all new cancer cases in the United States. It is an aggressive cancer with a high mortality and an average 5-year survival of 18.4%. […] Both of these are distinct entities with some overlap, with regards to epidemiologic distribution, risk factors, pathogenesis, and clinical and prognostic relevance. […] The decrease in ESCC is probably due to decrease in alcohol and tobacco abuse, while the increase in EAC is linked to increase in obesity and GERD. […] The most important etiological factor for EAC is Barretts esophagus in the setting of gastro-esophageal reflux.

• #2 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://www.wjgnet.com/1948-5204/full/v6/i5/112.htm

  Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most common histological type of esophageal cancer worldwide, with a higher incidence in developing nations. […] With the increased prevalence of gastroesophageal reflux disease and obesity in developed nations, the incidence of esophageal adenocarcinoma has dramatically increased in the past 40 years. […] The two most common histological types of esophageal carcinoma include SCC and adenocarcinoma. Less than 1% to 2% of all esophageal cancers are sarcomas or small cell carcinomas. Rarely lymphomas, carcinoids, and melanomas may arise in the esophagus. […] Major risk factors include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption may have a synergistic effect and increase the relative risk.

• #3 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  The two most common histological types of esophageal carcinoma include SCC and adenocarcinoma. Less than 1% to 2% of all esophageal cancers are sarcomas or small cell carcinomas. Rarely lymphomas, carcinoids, and melanomas may arise in the esophagus. […] SCC is the most common type of esophageal cancer worldwide. The overall incidence increases with age, reaching a peak in the seventh decade. SCC occurs equally as often in the middle and lower esophagus, with an incidence that is three times higher in blacks in comparison to whites. […] Major risk factors include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption may have a synergistic effect and increase the relative risk. The relative risk in men who used both heavy tobacco and alcohol was 35.4 in white males and 149.2 in black males compared to men of the same race and region who were non-smokers or drinkers. The mechanism of how tobacco and alcohol in combination lead to increased risk of esophageal cancer has been extensively studied. Alcohol can damage the cellular DNA by decreasing metabolic activity within the cell and therefore reduce detoxification function while promoting oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the hazardous carcinogens within tobacco are able to penetrate the esophageal epithelium easier. Some of the carcinogens in tobacco include aromatic amines, nitrosamines, polycyclic aromatic hydrocarbons, aldehydes and phenols.

• #4 Esophageal Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459267/

  Esophageal cancer is classified into 2 main types based on histologic features: squamous cell carcinoma and adenocarcinoma. In recent decades, the incidence of esophageal squamous cell carcinoma has decreased. In contrast, esophageal adenocarcinoma has risen significantly in the United States, particularly in the distal esophagus and gastroesophageal junction, mainly due to the prevalence of Barrett’s esophagus. […] Risk factors for esophageal squamous cell carcinoma include smoking, alcohol consumption, and a diet low in fruits and vegetables. In contrast, esophageal adenocarcinoma high-risk factors include Barrett esophagus, smoking, high body mass index, and gastroesophageal reflux disease. […] The pathophysiology of esophageal SCC consists of a complex interaction between genetic, environmental, and lifestyle factors. Chronic irritation and inflammation caused by smoking, alcohol consumption, hot beverages, and poor nutrition can damage the esophageal mucosa. This chronic inflammation, along with exposure to carcinogens, can lead to genetic alterations, such as mutations in tumor suppressor genes (eg, p53) and oncogenes (eg, cyclin D1), disrupting normal cell cycle regulation and promoting uncontrolled cell growth.

• #5 Oesophageal Cancer

  https://oncologypro.esmo.org/education-library/esmo-books/essentials-for-clinicians/gastrointestinal-tract-tumours-essentials-for-clinicians/oesophageal-cancer

  Oesophageal cancer (OC) comprises two distinct diseases: oesophageal squamous cell carcinoma (OSCC) and oesophageal adenocarcinoma (OAC), each with different risk factors and incidence trends. […] Whereas OSCC incidence is declining, the incidence of OAC is rising in developed countries, such as Canada, USA (White population) and Scotland. […] Precursor dysplastic lesions are detectable for OAC/OSCC. Repeated exposure to high-temperature drinks or gastro-oesophageal reflux disease (GORD) may cause inflammation. […] Barretts oesophagus (BE) is a probable intermediate stage between GORD and OAC, in which squamous cells are replaced by columnar epithelial cells, due to chronic injury. […] OACs arise from glandular cells at the lower end of oesophagus. OSCCs arise from epithelial cells that are exposed to irritation and carcinogens in foods and drinks.

• #6 Pathology of esophageal cancer and Barrett’s esophagus – Jain- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/14047/html

  Esophageal cancer is a serious malignancy with high mortality. The two common distinctive pathologic subtypes of esophageal cancer are squamous cell carcinoma and adenocarcinoma. These differ with regards to etiology, ethnic distribution, pathogenesis, and location in the esophagus. […] Esophageal cancer represents 1% of all new cancer cases in the United States. It is an aggressive cancer with a high mortality and an average 5-year survival of 18.4%. […] Both of these are distinct entities with some overlap, with regards to epidemiologic distribution, risk factors, pathogenesis, and clinical and prognostic relevance. […] The decrease in ESCC is probably due to decrease in alcohol and tobacco abuse, while the increase in EAC is linked to increase in obesity and GERD. […] The most important etiological factor for EAC is Barretts esophagus in the setting of gastro-esophageal reflux.

• #7 Esophageal Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459267/

  Esophageal cancer is classified into 2 main types based on histologic features: squamous cell carcinoma and adenocarcinoma. In recent decades, the incidence of esophageal squamous cell carcinoma has decreased. In contrast, esophageal adenocarcinoma has risen significantly in the United States, particularly in the distal esophagus and gastroesophageal junction, mainly due to the prevalence of Barrett’s esophagus. […] Risk factors for esophageal squamous cell carcinoma include smoking, alcohol consumption, and a diet low in fruits and vegetables. In contrast, esophageal adenocarcinoma high-risk factors include Barrett esophagus, smoking, high body mass index, and gastroesophageal reflux disease. […] The pathophysiology of esophageal SCC consists of a complex interaction between genetic, environmental, and lifestyle factors. Chronic irritation and inflammation caused by smoking, alcohol consumption, hot beverages, and poor nutrition can damage the esophageal mucosa. This chronic inflammation, along with exposure to carcinogens, can lead to genetic alterations, such as mutations in tumor suppressor genes (eg, p53) and oncogenes (eg, cyclin D1), disrupting normal cell cycle regulation and promoting uncontrolled cell growth.

• #8 Pathology Outlines – Squamous cell carcinoma

  https://www.pathologyoutlines.com/topic/esophagusscc.html

  Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer worldwide […] Distinct from esophageal adenocarcinoma in terms of cell origin, epidemiology, etiology, pathogenesis and location in the esophagus […] Develops by stepwise progression, with accumulating genetic abnormalities driving progression from histologically normal squamous mucosa to low grade intraepithelial neoplasia (dysplasia) to high grade intraepithelial neoplasia and finally to invasive squamous cell carcinoma […] TP53 mutation is a key early driver mutation developing at the stage of intraepithelial neoplasia […] Other key genetic abnormalities, including cell cycle regulators (e.g., CDKN2A [p16], RB1, NFE2L2, CHECK1, CHECK2, CCND1, CKD4, CDK6 and MDM2), EGFR signaling pathway, PI3Kinase signaling pathway, histone modification, NOTCH and WNT pathway, Hedgehog signaling and other genetic changes, including aneuploidy, copy number alterations

• #9 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  The two most common histological types of esophageal carcinoma include SCC and adenocarcinoma. Less than 1% to 2% of all esophageal cancers are sarcomas or small cell carcinomas. Rarely lymphomas, carcinoids, and melanomas may arise in the esophagus. […] SCC is the most common type of esophageal cancer worldwide. The overall incidence increases with age, reaching a peak in the seventh decade. SCC occurs equally as often in the middle and lower esophagus, with an incidence that is three times higher in blacks in comparison to whites. […] Major risk factors include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption may have a synergistic effect and increase the relative risk. The relative risk in men who used both heavy tobacco and alcohol was 35.4 in white males and 149.2 in black males compared to men of the same race and region who were non-smokers or drinkers. The mechanism of how tobacco and alcohol in combination lead to increased risk of esophageal cancer has been extensively studied. Alcohol can damage the cellular DNA by decreasing metabolic activity within the cell and therefore reduce detoxification function while promoting oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the hazardous carcinogens within tobacco are able to penetrate the esophageal epithelium easier. Some of the carcinogens in tobacco include aromatic amines, nitrosamines, polycyclic aromatic hydrocarbons, aldehydes and phenols.

• #10 Esophageal Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/277930-overview

  Major risk factors for SCC include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption can have a synergistic effect. […] Alcohol damages the cellular DNA by decreasing metabolic activity within the cell and therefore inhibits detoxification and promotes oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the carcinogens within tobacco are able to penetrate the esophageal epithelium more easily. […] The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant transformation. […] Adenocarcinoma of the esophagus most commonly occurs in the distal esophagus and has a distinct relationship to GERD. Untreated GERD can progress to Barrett esophagus (BE), in which the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium.

• #11 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  The two most common histological types of esophageal carcinoma include SCC and adenocarcinoma. Less than 1% to 2% of all esophageal cancers are sarcomas or small cell carcinomas. Rarely lymphomas, carcinoids, and melanomas may arise in the esophagus. […] SCC is the most common type of esophageal cancer worldwide. The overall incidence increases with age, reaching a peak in the seventh decade. SCC occurs equally as often in the middle and lower esophagus, with an incidence that is three times higher in blacks in comparison to whites. […] Major risk factors include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption may have a synergistic effect and increase the relative risk. The relative risk in men who used both heavy tobacco and alcohol was 35.4 in white males and 149.2 in black males compared to men of the same race and region who were non-smokers or drinkers. The mechanism of how tobacco and alcohol in combination lead to increased risk of esophageal cancer has been extensively studied. Alcohol can damage the cellular DNA by decreasing metabolic activity within the cell and therefore reduce detoxification function while promoting oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the hazardous carcinogens within tobacco are able to penetrate the esophageal epithelium easier. Some of the carcinogens in tobacco include aromatic amines, nitrosamines, polycyclic aromatic hydrocarbons, aldehydes and phenols.

• #12 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://www.wjgnet.com/1948-5204/full/v6/i5/112.htm

  The mechanism of how tobacco and alcohol in combination lead to increased risk of esophageal cancer has been extensively studied. Alcohol can damage the cellular DNA by decreasing metabolic activity within the cell and therefore reduce detoxification function while promoting oxidation. […] Other carcinogens, such as nitrosamines found in certain salted vegetables and preserved fish, have also been implicated in SCC of the esophagus. The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant change. […] Adenocarcinoma of the esophagus occurs in the distal esophagus approximately three-fourths of the time and has a distinct link to gastroesophageal reflux disease (GERD). Untreated GERD can progress to Barretts esophagus (BE), where the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium.

• #13 Esophageal Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/277930-overview

  Major risk factors for SCC include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption can have a synergistic effect. […] Alcohol damages the cellular DNA by decreasing metabolic activity within the cell and therefore inhibits detoxification and promotes oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the carcinogens within tobacco are able to penetrate the esophageal epithelium more easily. […] The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant transformation. […] Adenocarcinoma of the esophagus most commonly occurs in the distal esophagus and has a distinct relationship to GERD. Untreated GERD can progress to Barrett esophagus (BE), in which the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium.

• #14 Pathogenesis of Esophageal Cancer | Oncohema Key

  https://oncohemakey.com/pathogenesis-of-esophageal-cancer/

  The acetaldehyde generated by alcohol dehydrogenase has been shown to be carcinogenic in squamous cell carcinoma of the esophagus. […] Acetaldehyde forms covalent bonds with DNA, and the resulting DNA adducts can escape cellular DNA repair mechanisms causing detrimental mutations in growth-regulating genes. […] Chemical injury from a caustic chemical, such as lye, leads to fibrosis with stricture of the esophagus in the area of injury. […] The mechanism of inactivation occurs through silencing of the gene, by promoter methylation, or silencing through genome instability/chromosome translocations. […] The development of squamous cell carcinoma of the esophagus is strongly associated with low income. […] The incidence of adenocarcinoma of the esophagus has been increasing in Western countries over the last few decades.

• #15 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  The two most common histological types of esophageal carcinoma include SCC and adenocarcinoma. Less than 1% to 2% of all esophageal cancers are sarcomas or small cell carcinomas. Rarely lymphomas, carcinoids, and melanomas may arise in the esophagus. […] SCC is the most common type of esophageal cancer worldwide. The overall incidence increases with age, reaching a peak in the seventh decade. SCC occurs equally as often in the middle and lower esophagus, with an incidence that is three times higher in blacks in comparison to whites. […] Major risk factors include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption may have a synergistic effect and increase the relative risk. The relative risk in men who used both heavy tobacco and alcohol was 35.4 in white males and 149.2 in black males compared to men of the same race and region who were non-smokers or drinkers. The mechanism of how tobacco and alcohol in combination lead to increased risk of esophageal cancer has been extensively studied. Alcohol can damage the cellular DNA by decreasing metabolic activity within the cell and therefore reduce detoxification function while promoting oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the hazardous carcinogens within tobacco are able to penetrate the esophageal epithelium easier. Some of the carcinogens in tobacco include aromatic amines, nitrosamines, polycyclic aromatic hydrocarbons, aldehydes and phenols.

• #16 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://www.wjgnet.com/1948-5204/full/v6/i5/112.htm

  The mechanism of how tobacco and alcohol in combination lead to increased risk of esophageal cancer has been extensively studied. Alcohol can damage the cellular DNA by decreasing metabolic activity within the cell and therefore reduce detoxification function while promoting oxidation. […] Other carcinogens, such as nitrosamines found in certain salted vegetables and preserved fish, have also been implicated in SCC of the esophagus. The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant change. […] Adenocarcinoma of the esophagus occurs in the distal esophagus approximately three-fourths of the time and has a distinct link to gastroesophageal reflux disease (GERD). Untreated GERD can progress to Barretts esophagus (BE), where the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium.

• #17 Esophageal Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/277930-overview

  Major risk factors for SCC include alcohol consumption and tobacco use. Most studies have shown that alcohol is the primary risk factor but smoking in combination with alcohol consumption can have a synergistic effect. […] Alcohol damages the cellular DNA by decreasing metabolic activity within the cell and therefore inhibits detoxification and promotes oxidation. Alcohol is a solvent, specifically of fat-soluble compounds. Therefore, the carcinogens within tobacco are able to penetrate the esophageal epithelium more easily. […] The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant transformation. […] Adenocarcinoma of the esophagus most commonly occurs in the distal esophagus and has a distinct relationship to GERD. Untreated GERD can progress to Barrett esophagus (BE), in which the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium.

• #18 Pathogenesis of Esophageal Cancer | Encyclopedia MDPI

  https://encyclopedia.pub/entry/25063

  Esophageal cancer is rapidly increasing across the world. It is the sixth most common cause of death from cancer and is the eighth most common cancer worldwide. Esophageal cancer is a devastating malignancy which can be detected at an early stage but is more often diagnosed as an advanced process. It affects both men and women and inflicts the young and the elderly. There are multiple underlying factors involved in the pathogenesis of this cancer including inflammation. […] Smoking generates a pro-inflammatory response with production of several inflammatory cytokines and molecules. It promotes an inflammatory state by inducing the generation of cytokines such as interleukin (IL)-1, IL-6 and IL-8 and tumor necrosis factor-α (TNF-α). […] Continuous exposure to inflammation causes the production of substances such as cytokines, chemokines, and reactive oxygen species that can induce harmful effects. They can ultimately lead to augmentation of cell growth, stimulate invasion and promote the growth of blood vessels. Inflammatory cells may also produce mediators that can inhibit immune functions, and this also promotes carcinogenesis. […] Changes at the genome level are known to play a part in the pathogenesis of esophageal cancer. Genes that regulate the cell cycle are mutated (such as CDKN2A, NFE2L2, RB1, CHEK1, CHEK2) or are over-expressed (such as CCND1, CDK4/CDK6, MDM2) in cases of ESCC.

• #19 Pathology Outlines – Squamous cell carcinoma

  https://www.pathologyoutlines.com/topic/esophagusscc.html

  Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer worldwide […] Distinct from esophageal adenocarcinoma in terms of cell origin, epidemiology, etiology, pathogenesis and location in the esophagus […] Develops by stepwise progression, with accumulating genetic abnormalities driving progression from histologically normal squamous mucosa to low grade intraepithelial neoplasia (dysplasia) to high grade intraepithelial neoplasia and finally to invasive squamous cell carcinoma […] TP53 mutation is a key early driver mutation developing at the stage of intraepithelial neoplasia […] Other key genetic abnormalities, including cell cycle regulators (e.g., CDKN2A [p16], RB1, NFE2L2, CHECK1, CHECK2, CCND1, CKD4, CDK6 and MDM2), EGFR signaling pathway, PI3Kinase signaling pathway, histone modification, NOTCH and WNT pathway, Hedgehog signaling and other genetic changes, including aneuploidy, copy number alterations

• #20 Pathology Outlines – Squamous cell carcinoma

  https://www.pathologyoutlines.com/topic/esophagusscc.html

  Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer worldwide […] Distinct from esophageal adenocarcinoma in terms of cell origin, epidemiology, etiology, pathogenesis and location in the esophagus […] Develops by stepwise progression, with accumulating genetic abnormalities driving progression from histologically normal squamous mucosa to low grade intraepithelial neoplasia (dysplasia) to high grade intraepithelial neoplasia and finally to invasive squamous cell carcinoma […] TP53 mutation is a key early driver mutation developing at the stage of intraepithelial neoplasia […] Other key genetic abnormalities, including cell cycle regulators (e.g., CDKN2A [p16], RB1, NFE2L2, CHECK1, CHECK2, CCND1, CKD4, CDK6 and MDM2), EGFR signaling pathway, PI3Kinase signaling pathway, histone modification, NOTCH and WNT pathway, Hedgehog signaling and other genetic changes, including aneuploidy, copy number alterations

• #21 Mechanisms of Esophageal Carcinogenesis | Herbert Irving Comprehensive Cancer Center (HICCC) – New York

  https://www.cancer.columbia.edu/research/laboratories/rustgi-lab/mechanisms-esophageal-carcinogenesis

  Esophageal cancer is common worldwide. There are two major subtypes: esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC). Precursor lesions include esophageal squamous dysplasia and esophageal intestinal metaplasia (Barrett’s Esophagus), respectively. The molecular pathogenesis of ESCC and EAC involves genomic aberrations (e.g. cyclin D1, cyclin E, epidermal growth factor receptor or EGFR), genetic mutations or loss (e.g. TP53, p120catenin), epigenetic alterations, transcriptome derangements and interplay with environmental/lifestyle variables. […] As our primary overarching objective, we have made significant progress in this integrated Program Project (P01) to the identification and characterization of mechanisms underlying the molecular pathogenesis of ESCC and EAC as related to genomic and genetic divers in tumor cells, novel interactions in the tumor microenvironment and approaches to tumor metastasis.

• #22 Pathogenesis of Esophageal Cancer | Encyclopedia MDPI

  https://encyclopedia.pub/entry/25063

  Esophageal cancer is rapidly increasing across the world. It is the sixth most common cause of death from cancer and is the eighth most common cancer worldwide. Esophageal cancer is a devastating malignancy which can be detected at an early stage but is more often diagnosed as an advanced process. It affects both men and women and inflicts the young and the elderly. There are multiple underlying factors involved in the pathogenesis of this cancer including inflammation. […] Smoking generates a pro-inflammatory response with production of several inflammatory cytokines and molecules. It promotes an inflammatory state by inducing the generation of cytokines such as interleukin (IL)-1, IL-6 and IL-8 and tumor necrosis factor-α (TNF-α). […] Continuous exposure to inflammation causes the production of substances such as cytokines, chemokines, and reactive oxygen species that can induce harmful effects. They can ultimately lead to augmentation of cell growth, stimulate invasion and promote the growth of blood vessels. Inflammatory cells may also produce mediators that can inhibit immune functions, and this also promotes carcinogenesis. […] Changes at the genome level are known to play a part in the pathogenesis of esophageal cancer. Genes that regulate the cell cycle are mutated (such as CDKN2A, NFE2L2, RB1, CHEK1, CHEK2) or are over-expressed (such as CCND1, CDK4/CDK6, MDM2) in cases of ESCC.

• #23 Gene function analysis and underlying mechanism of esophagus cancer based on microarray gene expression profiling | Oncotarget

  https://www.oncotarget.com/article/22160/text/

  Esophageal cancer (EC) is one of the most common digestive malignant tumors worldwide. […] New targets and novel therapies are needed to improve outcomes for these patients. This study aimed to explore the molecular mechanisms of EC by integrated bioinformatic analyses of the feature genes associated with EC and correlative gene functions which can distinguish cancerous tissues from non-cancerous tissues. […] The results showed that DEGs mainly participated in the process of cell adhesion, cell proliferation, survival, invasion, metastasis and angiogenesis. Aberrant expression of PTK2, MAPK signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway and MET were closely associated with EC carcinogenesis. Importantly, Interleukin 8 (IL8) and C-X-C chemokine receptor type 7 (CXCR-7) were predicted to be significantly related to EC.

• #24 Esophageal Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459267/

  In contrast, the pathophysiologic mechanism of esophageal adenocarcinoma is repeated exposure of the lower esophagus to stomach acid secondary to chronic GERD, which leads to the replacement of the normal squamous epithelium with metaplastic columnar epithelium (ie, Barrett esophagus). The metaplastic epithelium may progressively undergo dysplastic changes, classified as low-grade or high-grade dysplasia, based on the degree of cellular abnormalities. High-grade dysplasia can progress to invasive adenocarcinoma, where cancer cells invade the underlying layers of the esophageal wall.

• #25 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  Other carcinogens, such as nitrosamines found in certain salted vegetables and preserved fish, have also been implicated in SCC of the esophagus. The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant change. […] Adenocarcinoma of the esophagus occurs in the distal esophagus approximately three-fourths of the time and has a distinct link to gastroesophageal reflux disease (GERD). Untreated GERD can progress to Barretts esophagus (BE), where the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium. The chronic reflux of gastric acid and bile at the gastroesophageal junction and the subsequent damage to the esophagus has been implicated in the pathogenesis of Barrett metaplasia.

• #26 Pathology of esophageal cancer and Barrett’s esophagus – Jain- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/14047/html

  Barretts esophagus is essentially defined as columnar metaplasia that replaces the stratified squamous epithelium of the distal esophagus, and has a predisposition to develop adenocarcinoma. […] The development of EAC appears to occur through progressive accumulation of multiple genetic abnormalities such as mutational inactivation of p16, and p53 genes, cell cycle abnormalities and aneuploidy. The molecular mechanism is complex and cannot be attributed to a single genetic event.

• #27 Esophageal Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459267/

  In contrast, the pathophysiologic mechanism of esophageal adenocarcinoma is repeated exposure of the lower esophagus to stomach acid secondary to chronic GERD, which leads to the replacement of the normal squamous epithelium with metaplastic columnar epithelium (ie, Barrett esophagus). The metaplastic epithelium may progressively undergo dysplastic changes, classified as low-grade or high-grade dysplasia, based on the degree of cellular abnormalities. High-grade dysplasia can progress to invasive adenocarcinoma, where cancer cells invade the underlying layers of the esophageal wall.

• #28 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://www.wjgnet.com/1948-5204/full/v6/i5/112.htm

  The mechanism of how tobacco and alcohol in combination lead to increased risk of esophageal cancer has been extensively studied. Alcohol can damage the cellular DNA by decreasing metabolic activity within the cell and therefore reduce detoxification function while promoting oxidation. […] Other carcinogens, such as nitrosamines found in certain salted vegetables and preserved fish, have also been implicated in SCC of the esophagus. The pathogenesis appears to be linked to inflammation of the squamous epithelium that leads to dysplasia and in situ malignant change. […] Adenocarcinoma of the esophagus occurs in the distal esophagus approximately three-fourths of the time and has a distinct link to gastroesophageal reflux disease (GERD). Untreated GERD can progress to Barretts esophagus (BE), where the stratified squamous epithelium that normally lines the esophagus is replaced by a columnar epithelium.

• #29 Esophageal Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/277930-overview

  The chronic reflux of gastric acid and bile at the gastroesophageal junction and the subsequent damage to the esophagus has been implicated in the pathogenesis of Barrett metaplasia. […] The progression of Barrett metaplasia to adenocarcinoma is associated with several changes in gene structure, gene expression, and protein structure. […] Obesity is another risk factor for esophageal adenocarcinoma, specifically in individuals with central fat distribution. […] Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines.

• #30 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  The presence of lipopolysaccharide (LPS) on the surface of Gram-negative bacteria activates the NF-B pathway, leading to elevated expression of IL-8, which is a significant event in the transition from a normal esophagus to BE. […] A study that involved BE and EAC patients in different stages of disease did not demonstrate a significant difference in the alpha diversities. […] Snider et al. reported a notable decrease in alpha diversity in high-grade intraepithelial neoplasia and adenocarcinoma compared to non-cancerous esophageal tissue. […] The presence of H. pylori can influence the microbial composition of the lower esophagus. […] H. pylori infection might be a protective factor against the development of EAC. […] These findings suggested that P. gingivalis could serve as a novel prognostic indicator for ESCC.

• #31 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  The risk of developing esophageal cancer is 50-100 times more likely in those patients with BE. However, a majority of patients with BE will not develop EAC, the annual risk in patients with BE has been reported as 0.12%. […] Another risk factor for EAC is obesity, specifically in those individuals with predominately abdominal centered fat distribution. Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines. Adipocytes in the tumor microenvironment supply energy production and support tumor growth and progression. […] Long-term prognosis after resection is better for adenocarcinoma compared to SCC. A study by Siewert et al. of 1059 patients who underwent resection showed the overall 5-year survival rate for the adenocarcinoma group was 47% in comparison to 37% for the group with SCC.

• #32 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://www.wjgnet.com/1948-5204/full/v6/i5/112.htm

  The chronic reflux of gastric acid and bile at the gastroesophageal junction and the subsequent damage to the esophagus has been implicated in the pathogenesis of Barrett metaplasia. […] The risk of developing esophageal cancer is 50-100 times more likely in those patients with BE. However, a majority of patients with BE will not develop EAC, the annual risk in patients with BE has been reported as 0.12%. […] Another risk factor for EAC is obesity, specifically in those individuals with predominately abdominal centered fat distribution. Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines. […] Long-term prognosis after resection is better for adenocarcinoma compared to SCC.

• #33 Esophageal Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459267/

  Esophageal cancer is classified into 2 main types based on histologic features: squamous cell carcinoma and adenocarcinoma. In recent decades, the incidence of esophageal squamous cell carcinoma has decreased. In contrast, esophageal adenocarcinoma has risen significantly in the United States, particularly in the distal esophagus and gastroesophageal junction, mainly due to the prevalence of Barrett’s esophagus. […] Risk factors for esophageal squamous cell carcinoma include smoking, alcohol consumption, and a diet low in fruits and vegetables. In contrast, esophageal adenocarcinoma high-risk factors include Barrett esophagus, smoking, high body mass index, and gastroesophageal reflux disease. […] The pathophysiology of esophageal SCC consists of a complex interaction between genetic, environmental, and lifestyle factors. Chronic irritation and inflammation caused by smoking, alcohol consumption, hot beverages, and poor nutrition can damage the esophageal mucosa. This chronic inflammation, along with exposure to carcinogens, can lead to genetic alterations, such as mutations in tumor suppressor genes (eg, p53) and oncogenes (eg, cyclin D1), disrupting normal cell cycle regulation and promoting uncontrolled cell growth.

• #34 Oesophageal Cancer

  https://oncologypro.esmo.org/education-library/esmo-books/essentials-for-clinicians/gastrointestinal-tract-tumours-essentials-for-clinicians/oesophageal-cancer

  Smoking, low fruit and vegetable intake and high intake of processed meat increase the risk of both OSCC and OAC. Alcohol consumption only increases the risk of OSCC. […] Hot beverages increase the risk of both. Human papillomavirus (HPV) 16 infection may increase the risk of OSCC, while Helicobacter pylori (H. pylori) infection may reduce the risk of OAC. Obesity, GORD and BE increase the risk of OAC. […] Genome-wide association studies (GWAS) of OSCC in Chinese populations showed associations with different single nucleotide polymorphisms (SNPs). The Cancer Genome Atlas (TCGA) showed genomic amplification of different chromosomes.

• #35 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  The risk of developing esophageal cancer is 50-100 times more likely in those patients with BE. However, a majority of patients with BE will not develop EAC, the annual risk in patients with BE has been reported as 0.12%. […] Another risk factor for EAC is obesity, specifically in those individuals with predominately abdominal centered fat distribution. Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines. Adipocytes in the tumor microenvironment supply energy production and support tumor growth and progression. […] Long-term prognosis after resection is better for adenocarcinoma compared to SCC. A study by Siewert et al. of 1059 patients who underwent resection showed the overall 5-year survival rate for the adenocarcinoma group was 47% in comparison to 37% for the group with SCC.

• #36 Esophageal Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/277930-overview

  The chronic reflux of gastric acid and bile at the gastroesophageal junction and the subsequent damage to the esophagus has been implicated in the pathogenesis of Barrett metaplasia. […] The progression of Barrett metaplasia to adenocarcinoma is associated with several changes in gene structure, gene expression, and protein structure. […] Obesity is another risk factor for esophageal adenocarcinoma, specifically in individuals with central fat distribution. […] Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines.

• #37 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  The risk of developing esophageal cancer is 50-100 times more likely in those patients with BE. However, a majority of patients with BE will not develop EAC, the annual risk in patients with BE has been reported as 0.12%. […] Another risk factor for EAC is obesity, specifically in those individuals with predominately abdominal centered fat distribution. Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines. Adipocytes in the tumor microenvironment supply energy production and support tumor growth and progression. […] Long-term prognosis after resection is better for adenocarcinoma compared to SCC. A study by Siewert et al. of 1059 patients who underwent resection showed the overall 5-year survival rate for the adenocarcinoma group was 47% in comparison to 37% for the group with SCC.

• #38 Pathology of esophageal cancer and Barrett’s esophagus – Jain- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/14047/html

  Barretts esophagus is essentially defined as columnar metaplasia that replaces the stratified squamous epithelium of the distal esophagus, and has a predisposition to develop adenocarcinoma. […] The development of EAC appears to occur through progressive accumulation of multiple genetic abnormalities such as mutational inactivation of p16, and p53 genes, cell cycle abnormalities and aneuploidy. The molecular mechanism is complex and cannot be attributed to a single genetic event.

• #39 Pathology of esophageal cancer and Barrett’s esophagus – Jain- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/14047/html

  Barretts esophagus is essentially defined as columnar metaplasia that replaces the stratified squamous epithelium of the distal esophagus, and has a predisposition to develop adenocarcinoma. […] The development of EAC appears to occur through progressive accumulation of multiple genetic abnormalities such as mutational inactivation of p16, and p53 genes, cell cycle abnormalities and aneuploidy. The molecular mechanism is complex and cannot be attributed to a single genetic event.

• #40 Pathogenesis of Esophageal Cancer | Oncohema Key

  https://oncohemakey.com/pathogenesis-of-esophageal-cancer/

  Three candidate genes containing germline mutations were identified in patients with esophageal adenocarcinoma: MSR1, ASCC1, and CTHRC1. […] The single-nucleotide polymorphism, IL-18-607 C/A in its promoter, is associated with the development of Barretts esophagus and esophageal adenocarcinoma. […] Gastroesophageal reflux is an important risk factor for the development of esophageal adenocarcinoma. […] Obesity is a strong risk factor for developing esophageal adenocarcinoma. […] Helicobacter pylori infection occurs in 50 % of the worldwide population and commonly colonizes the stomach of children.

• #41 Pathogenesis of Esophageal Cancer | Oncohema Key

  https://oncohemakey.com/pathogenesis-of-esophageal-cancer/

  Three candidate genes containing germline mutations were identified in patients with esophageal adenocarcinoma: MSR1, ASCC1, and CTHRC1. […] The single-nucleotide polymorphism, IL-18-607 C/A in its promoter, is associated with the development of Barretts esophagus and esophageal adenocarcinoma. […] Gastroesophageal reflux is an important risk factor for the development of esophageal adenocarcinoma. […] Obesity is a strong risk factor for developing esophageal adenocarcinoma. […] Helicobacter pylori infection occurs in 50 % of the worldwide population and commonly colonizes the stomach of children.

• #42 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  The presence of lipopolysaccharide (LPS) on the surface of Gram-negative bacteria activates the NF-B pathway, leading to elevated expression of IL-8, which is a significant event in the transition from a normal esophagus to BE. […] A study that involved BE and EAC patients in different stages of disease did not demonstrate a significant difference in the alpha diversities. […] Snider et al. reported a notable decrease in alpha diversity in high-grade intraepithelial neoplasia and adenocarcinoma compared to non-cancerous esophageal tissue. […] The presence of H. pylori can influence the microbial composition of the lower esophagus. […] H. pylori infection might be a protective factor against the development of EAC. […] These findings suggested that P. gingivalis could serve as a novel prognostic indicator for ESCC.

• #43 Pathogenesis of Esophageal Cancer | Oncohema Key

  https://oncohemakey.com/pathogenesis-of-esophageal-cancer/

  Three candidate genes containing germline mutations were identified in patients with esophageal adenocarcinoma: MSR1, ASCC1, and CTHRC1. […] The single-nucleotide polymorphism, IL-18-607 C/A in its promoter, is associated with the development of Barretts esophagus and esophageal adenocarcinoma. […] Gastroesophageal reflux is an important risk factor for the development of esophageal adenocarcinoma. […] Obesity is a strong risk factor for developing esophageal adenocarcinoma. […] Helicobacter pylori infection occurs in 50 % of the worldwide population and commonly colonizes the stomach of children.

• #44 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. […] Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. […] Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients. […] The potential contribution of esophageal microorganisms to the development of EC has yet to be fully elucidated. […] Prolonged adherence to an urban-style diet can lead to chronic esophageal inflammation and dysbiosis, potentially contributing to the progression of esophageal diseases. […] Acid reflux-induced inflammation and mucosal damage can lead to GERD and subsequent replacement of the original esophageal squamous epithelium with columnar epithelium that has the potential to progress to BE.

• #45 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/early/2023/10/09/j.issn.2095-3941.2023.0177

  Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. […] Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. […] Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients. […] The presence of lipopolysaccharide (LPS) on the surface of Gram-negative bacteria activates the NF-B pathway, leading to elevated expression of IL-8, which is a significant event in the transition from a normal esophagus to BE. […] Taken together, these studies suggest that BE-induced microbiome changes in the esophagus may contribute to the development of EAC.

• #46 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. […] Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. […] Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients. […] The potential contribution of esophageal microorganisms to the development of EC has yet to be fully elucidated. […] Prolonged adherence to an urban-style diet can lead to chronic esophageal inflammation and dysbiosis, potentially contributing to the progression of esophageal diseases. […] Acid reflux-induced inflammation and mucosal damage can lead to GERD and subsequent replacement of the original esophageal squamous epithelium with columnar epithelium that has the potential to progress to BE.

• #47 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. […] Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. […] Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients. […] The potential contribution of esophageal microorganisms to the development of EC has yet to be fully elucidated. […] Prolonged adherence to an urban-style diet can lead to chronic esophageal inflammation and dysbiosis, potentially contributing to the progression of esophageal diseases. […] Acid reflux-induced inflammation and mucosal damage can lead to GERD and subsequent replacement of the original esophageal squamous epithelium with columnar epithelium that has the potential to progress to BE.

• #48 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  The presence of lipopolysaccharide (LPS) on the surface of Gram-negative bacteria activates the NF-B pathway, leading to elevated expression of IL-8, which is a significant event in the transition from a normal esophagus to BE. […] A study that involved BE and EAC patients in different stages of disease did not demonstrate a significant difference in the alpha diversities. […] Snider et al. reported a notable decrease in alpha diversity in high-grade intraepithelial neoplasia and adenocarcinoma compared to non-cancerous esophageal tissue. […] The presence of H. pylori can influence the microbial composition of the lower esophagus. […] H. pylori infection might be a protective factor against the development of EAC. […] These findings suggested that P. gingivalis could serve as a novel prognostic indicator for ESCC.

• #49 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #50 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/early/2023/10/09/j.issn.2095-3941.2023.0177

  The tumor tissues of these affected patients have increased production of chemokines, which contributes to a more aggressive disease course and reduced survival. […] Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #51 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #52 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/early/2023/10/09/j.issn.2095-3941.2023.0177

  The tumor tissues of these affected patients have increased production of chemokines, which contributes to a more aggressive disease course and reduced survival. […] Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #53 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #54 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/early/2023/10/09/j.issn.2095-3941.2023.0177

  The tumor tissues of these affected patients have increased production of chemokines, which contributes to a more aggressive disease course and reduced survival. […] Therefore, it is reasonable to consider P. gingivalis as a promising target to prevent and/or treat P. gingivalis-infected patients with ESCC. […] Changes in the composition and abundance of esophageal microbiota could promote the development of EC in different ways. […] The involvement of disrupted cross-talk between esophageal microbiota and immune cells has been implicated in several signaling pathways known to contribute to the development of EC.

• #55 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Esophageal cancer (EC) is a disease often marked by aggressive growth and poor prognosis. […] The complex and dynamic interactions of the secreted cytokines, chemokines, growth factors, and their receptors mediate chronic inflammation and immunosuppressive TME favoring tumor progression, metastasis, and decreased response to therapy. […] This review highlighted the novel insights into the understanding and functional impact of deregulated cytokines and chemokines in imparting aggressive EC, stressing the nature and therapeutic consequences of the cytokine-chemokine network. […] We also discuss cytokine-chemokine oncogenic potential by contributing to the Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niche, and therapeutic resistance development.

• #56 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Recent studies have conclusively established an essential role of the tumor microenvironment (TME) in EC progression and metastasis. […] Their practical importance is in imparting an aggressive EC phenotype by contributing to Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niches, and therapeutic resistance. […] The cytokines and chemokines secreted by the immune cells mediate cancer-stromal interactions and activate several downstream effector pathways such as JAK/STAT, NF-, NOTCH to mediate various properties of cancer hallmarks. […] The CC chemokine, CCL5 (also known as RANTES), is a downstream target of the NF-B pathway known to promote tumor cell proliferation, invasion, and angiogenesis by facilitating the recruitment of eosinophils, monocytes, T cells, and basophils.

• #57 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Cytokines act as markers of metastasis and angiogenesis, the root cause of cancer mortality. […] Pro-inflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-) have been linked with EC pathogenesis. […] IL-1 is involved in promoting angiogenesis through the production of vascular endothelial growth factor (VEGF). […] The release of IL-1 from M2 macrophages associated with increased expression (phosphorylation) of both NF-B and IB suggests that IL-1 regulates EMT through the NF-B pathway. […] IL-6 and CXCR7 are also implicated in EMT through the NF-B signaling pathway. […] The inhibition of CXCR4 results in reduced expression of EMT genes in ESCC, which indicates that the increased expression of CXCR4 and CXCR7 are associated with poor prognosis in EC.

• #58 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Cytokines act as markers of metastasis and angiogenesis, the root cause of cancer mortality. […] Pro-inflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-) have been linked with EC pathogenesis. […] IL-1 is involved in promoting angiogenesis through the production of vascular endothelial growth factor (VEGF). […] The release of IL-1 from M2 macrophages associated with increased expression (phosphorylation) of both NF-B and IB suggests that IL-1 regulates EMT through the NF-B pathway. […] IL-6 and CXCR7 are also implicated in EMT through the NF-B signaling pathway. […] The inhibition of CXCR4 results in reduced expression of EMT genes in ESCC, which indicates that the increased expression of CXCR4 and CXCR7 are associated with poor prognosis in EC.

• #59 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Cytokines act as markers of metastasis and angiogenesis, the root cause of cancer mortality. […] Pro-inflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-) have been linked with EC pathogenesis. […] IL-1 is involved in promoting angiogenesis through the production of vascular endothelial growth factor (VEGF). […] The release of IL-1 from M2 macrophages associated with increased expression (phosphorylation) of both NF-B and IB suggests that IL-1 regulates EMT through the NF-B pathway. […] IL-6 and CXCR7 are also implicated in EMT through the NF-B signaling pathway. […] The inhibition of CXCR4 results in reduced expression of EMT genes in ESCC, which indicates that the increased expression of CXCR4 and CXCR7 are associated with poor prognosis in EC.

• #60 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Cytokines act as markers of metastasis and angiogenesis, the root cause of cancer mortality. […] Pro-inflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-) have been linked with EC pathogenesis. […] IL-1 is involved in promoting angiogenesis through the production of vascular endothelial growth factor (VEGF). […] The release of IL-1 from M2 macrophages associated with increased expression (phosphorylation) of both NF-B and IB suggests that IL-1 regulates EMT through the NF-B pathway. […] IL-6 and CXCR7 are also implicated in EMT through the NF-B signaling pathway. […] The inhibition of CXCR4 results in reduced expression of EMT genes in ESCC, which indicates that the increased expression of CXCR4 and CXCR7 are associated with poor prognosis in EC.

• #61 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Cytokines act as markers of metastasis and angiogenesis, the root cause of cancer mortality. […] Pro-inflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-) have been linked with EC pathogenesis. […] IL-1 is involved in promoting angiogenesis through the production of vascular endothelial growth factor (VEGF). […] The release of IL-1 from M2 macrophages associated with increased expression (phosphorylation) of both NF-B and IB suggests that IL-1 regulates EMT through the NF-B pathway. […] IL-6 and CXCR7 are also implicated in EMT through the NF-B signaling pathway. […] The inhibition of CXCR4 results in reduced expression of EMT genes in ESCC, which indicates that the increased expression of CXCR4 and CXCR7 are associated with poor prognosis in EC.

• #62 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Furthermore, the induction of IL-6 is found to increase the expression of ALDH1, a CSC marker, and TWIST, an essential EMT inducer, in a xenograft tumor model. […] The elevated expression of MMP2, MMP7, MMP9, and vimentin and the reduced expression of E-cadherin in ALDH1A1high ESCC indicates a close relationship between EMT and ALDH1A1 expression. […] The CXCL12-CXCR4 axis regulates critical aspects such as cancer cell proliferation, chemotaxis, and invasion. […] Several studies indicated that the CXCL12-CXCR4 signaling axis is essential for aggressive EC behavior and poor prognosis. […] These findings suggest that this receptor may have an essential role in the early metastasis spread in EC. […] The accumulation of pro-inflammatory cytokines triggers an immunosuppressive TME leading to the attenuation of the innate and adaptive immune responses. […] Overall, these findings indicated that CXCL8 could be involved in the growth of ESCC as an autocrine/paracrine factor by increasing the migration and invasion of tumor cells.

• #63 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Furthermore, the induction of IL-6 is found to increase the expression of ALDH1, a CSC marker, and TWIST, an essential EMT inducer, in a xenograft tumor model. […] The elevated expression of MMP2, MMP7, MMP9, and vimentin and the reduced expression of E-cadherin in ALDH1A1high ESCC indicates a close relationship between EMT and ALDH1A1 expression. […] The CXCL12-CXCR4 axis regulates critical aspects such as cancer cell proliferation, chemotaxis, and invasion. […] Several studies indicated that the CXCL12-CXCR4 signaling axis is essential for aggressive EC behavior and poor prognosis. […] These findings suggest that this receptor may have an essential role in the early metastasis spread in EC. […] The accumulation of pro-inflammatory cytokines triggers an immunosuppressive TME leading to the attenuation of the innate and adaptive immune responses. […] Overall, these findings indicated that CXCL8 could be involved in the growth of ESCC as an autocrine/paracrine factor by increasing the migration and invasion of tumor cells.

• #64 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Furthermore, the induction of IL-6 is found to increase the expression of ALDH1, a CSC marker, and TWIST, an essential EMT inducer, in a xenograft tumor model. […] The elevated expression of MMP2, MMP7, MMP9, and vimentin and the reduced expression of E-cadherin in ALDH1A1high ESCC indicates a close relationship between EMT and ALDH1A1 expression. […] The CXCL12-CXCR4 axis regulates critical aspects such as cancer cell proliferation, chemotaxis, and invasion. […] Several studies indicated that the CXCL12-CXCR4 signaling axis is essential for aggressive EC behavior and poor prognosis. […] These findings suggest that this receptor may have an essential role in the early metastasis spread in EC. […] The accumulation of pro-inflammatory cytokines triggers an immunosuppressive TME leading to the attenuation of the innate and adaptive immune responses. […] Overall, these findings indicated that CXCL8 could be involved in the growth of ESCC as an autocrine/paracrine factor by increasing the migration and invasion of tumor cells.

• #65 Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-020-01294-3

  Furthermore, the induction of IL-6 is found to increase the expression of ALDH1, a CSC marker, and TWIST, an essential EMT inducer, in a xenograft tumor model. […] The elevated expression of MMP2, MMP7, MMP9, and vimentin and the reduced expression of E-cadherin in ALDH1A1high ESCC indicates a close relationship between EMT and ALDH1A1 expression. […] The CXCL12-CXCR4 axis regulates critical aspects such as cancer cell proliferation, chemotaxis, and invasion. […] Several studies indicated that the CXCL12-CXCR4 signaling axis is essential for aggressive EC behavior and poor prognosis. […] These findings suggest that this receptor may have an essential role in the early metastasis spread in EC. […] The accumulation of pro-inflammatory cytokines triggers an immunosuppressive TME leading to the attenuation of the innate and adaptive immune responses. […] Overall, these findings indicated that CXCL8 could be involved in the growth of ESCC as an autocrine/paracrine factor by increasing the migration and invasion of tumor cells.

• #66 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4021327/

  The risk of developing esophageal cancer is 50-100 times more likely in those patients with BE. However, a majority of patients with BE will not develop EAC, the annual risk in patients with BE has been reported as 0.12%. […] Another risk factor for EAC is obesity, specifically in those individuals with predominately abdominal centered fat distribution. Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines. Adipocytes in the tumor microenvironment supply energy production and support tumor growth and progression. […] Long-term prognosis after resection is better for adenocarcinoma compared to SCC. A study by Siewert et al. of 1059 patients who underwent resection showed the overall 5-year survival rate for the adenocarcinoma group was 47% in comparison to 37% for the group with SCC.

• #67 Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

  https://www.wjgnet.com/1948-5204/full/v6/i5/112.htm

  The chronic reflux of gastric acid and bile at the gastroesophageal junction and the subsequent damage to the esophagus has been implicated in the pathogenesis of Barrett metaplasia. […] The risk of developing esophageal cancer is 50-100 times more likely in those patients with BE. However, a majority of patients with BE will not develop EAC, the annual risk in patients with BE has been reported as 0.12%. […] Another risk factor for EAC is obesity, specifically in those individuals with predominately abdominal centered fat distribution. Hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low-grade inflammation and promote tumor development through the release of adipokines and cytokines. […] Long-term prognosis after resection is better for adenocarcinoma compared to SCC.

• #68 Pathogenesis and progression of oesophageal adenocarcinoma varies by prior diagnosis of Barrett’s oesophagus | British Journal of Cancer

  https://www.nature.com/articles/bjc2016344

  We have shown that, on average, EA-prior BE cases have lower risks of all-cause and oesophageal cancer-specific death relative to EA-no prior BE cases. […] However, this survival benefit is unlikely the result of surveillance endoscopydespite the greater proportion of EA-prior BE cases that were diagnosed with localised disease, relative to EA-no prior BE casesbecause analyses with additional adjustment for time to surgery (amongst those who received surgery) and restriction to those who did not receive surgery each provided similar survival benefits. […] In sum, our study provides evidence that EA case groups differ by whether or not they were previously diagnosed with BE, including differences in medical history (specifically GERD), clinical presentation and survival.

• #69 Pathogenesis and progression of oesophageal adenocarcinoma varies by prior diagnosis of Barrett’s oesophagus | British Journal of Cancer

  https://www.nature.com/articles/bjc2016344

  We have shown that, on average, EA-prior BE cases have lower risks of all-cause and oesophageal cancer-specific death relative to EA-no prior BE cases. […] However, this survival benefit is unlikely the result of surveillance endoscopydespite the greater proportion of EA-prior BE cases that were diagnosed with localised disease, relative to EA-no prior BE casesbecause analyses with additional adjustment for time to surgery (amongst those who received surgery) and restriction to those who did not receive surgery each provided similar survival benefits. […] In sum, our study provides evidence that EA case groups differ by whether or not they were previously diagnosed with BE, including differences in medical history (specifically GERD), clinical presentation and survival.

• #70 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/21/2/163

  Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. […] Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. […] Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients. […] The potential contribution of esophageal microorganisms to the development of EC has yet to be fully elucidated. […] Prolonged adherence to an urban-style diet can lead to chronic esophageal inflammation and dysbiosis, potentially contributing to the progression of esophageal diseases. […] Acid reflux-induced inflammation and mucosal damage can lead to GERD and subsequent replacement of the original esophageal squamous epithelium with columnar epithelium that has the potential to progress to BE.

• #71 Microbiome changes in esophageal cancer: implications for pathogenesis and prognosis | Cancer Biology & Medicine

  https://www.cancerbiomed.org/content/early/2023/10/09/j.issn.2095-3941.2023.0177

  Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. […] Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. […] Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients. […] The presence of lipopolysaccharide (LPS) on the surface of Gram-negative bacteria activates the NF-B pathway, leading to elevated expression of IL-8, which is a significant event in the transition from a normal esophagus to BE. […] Taken together, these studies suggest that BE-induced microbiome changes in the esophagus may contribute to the development of EAC.

• #72 Transcription Factors and MiRNAs Regulate the Mechanism of Drug Resistance in Oesophageal Cancer

  https://www.accscience.com/journal/CP/4/2/10.18063/cp.v4i2.367

  The presence of drug resistance can lead to differences in treatment outcomes among patients using the same drug. […] Identification of key biological markers associated with drug resistance can help clinicians to quickly select the appropriate drug to prolong the survival time of patients, and it is important for drug development and detailed study of the drugs mechanism of action. […] Thirteen drug resistance-associated modules were identified, each containing 1-6 drug resistance-associated key regulators. Among them, transcription factors SP1, has-miR-21-5p and hsa-miR-1-5p play key regulatory roles in the resistance modules of various drugs, and they regulate drug resistance-associated differentially expressed genes through one-step or multi-step regulatory relationships. […] Key transcription factors and miRNA in the transcriptional regulatory network that regulate drug resistance-associated genes can be used as potential biomarkers to identify drug resistance to the corresponding drugs in tumor patients.

• #73 Transcription Factors and MiRNAs Regulate the Mechanism of Drug Resistance in Oesophageal Cancer

  https://www.accscience.com/journal/CP/4/2/10.18063/cp.v4i2.367

  The presence of drug resistance can lead to differences in treatment outcomes among patients using the same drug. […] Identification of key biological markers associated with drug resistance can help clinicians to quickly select the appropriate drug to prolong the survival time of patients, and it is important for drug development and detailed study of the drugs mechanism of action. […] Thirteen drug resistance-associated modules were identified, each containing 1-6 drug resistance-associated key regulators. Among them, transcription factors SP1, has-miR-21-5p and hsa-miR-1-5p play key regulatory roles in the resistance modules of various drugs, and they regulate drug resistance-associated differentially expressed genes through one-step or multi-step regulatory relationships. […] Key transcription factors and miRNA in the transcriptional regulatory network that regulate drug resistance-associated genes can be used as potential biomarkers to identify drug resistance to the corresponding drugs in tumor patients.

• #74 Transcription Factors and MiRNAs Regulate the Mechanism of Drug Resistance in Oesophageal Cancer

  https://www.accscience.com/journal/CP/4/2/10.18063/cp.v4i2.367

  The presence of drug resistance can lead to differences in treatment outcomes among patients using the same drug. […] Identification of key biological markers associated with drug resistance can help clinicians to quickly select the appropriate drug to prolong the survival time of patients, and it is important for drug development and detailed study of the drugs mechanism of action. […] Thirteen drug resistance-associated modules were identified, each containing 1-6 drug resistance-associated key regulators. Among them, transcription factors SP1, has-miR-21-5p and hsa-miR-1-5p play key regulatory roles in the resistance modules of various drugs, and they regulate drug resistance-associated differentially expressed genes through one-step or multi-step regulatory relationships. […] Key transcription factors and miRNA in the transcriptional regulatory network that regulate drug resistance-associated genes can be used as potential biomarkers to identify drug resistance to the corresponding drugs in tumor patients.

• #75 Gene function analysis and underlying mechanism of esophagus cancer based on microarray gene expression profiling | Oncotarget

  https://www.oncotarget.com/article/22160/

  Esophageal cancer (EC) is one of the most common digestive malignant tumors worldwide. […] This study aimed to explore the molecular mechanisms of EC by integrated bioinformatic analyses of the feature genes associated with EC and correlative gene functions which can distinguish cancerous tissues from non-cancerous tissues. […] The results showed that DEGs mainly participated in the process of cell adhesion, cell proliferation, survival, invasion, metastasis and angiogenesis. […] Aberrant expression of PTK2, MAPK signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway and MET were closely associated with EC carcinogenesis. […] Importantly, Interleukin 8 (IL8) and C-X-C chemokine receptor type 7 (CXCR-7) were predicted to be significantly related to EC. […] Our discovery provides a registry of genes and pathways that are disrupted in EC, which has the potential to be used in clinic for diagnosis and target therapy of EC in future.

• #76 Gene function analysis and underlying mechanism of esophagus cancer based on microarray gene expression profiling | Oncotarget

  https://www.oncotarget.com/article/22160/text/

  Our results suggested that EC progression was strongly associated with (1) cell proliferation, survival, invasion, metastasis and angiogenesis (MAPK signaling pathway, cell cycle, wnt signaling pathway, VEGF-signaling pathway, MMP1, SPP1, COL11A1), (2) cell adhesion (focal adhesion, adhesion junction, calcium signaling pathway, PTK2), (3) the imbalance of oncogene and cancer suppressor gene (p53 signaling pathway, pathway in cancer, MET, PLCD1) as well as (4) the participation of the immune system (IL8, CXCR7). […] Our discovery may be of vital importance for investigating the complex interacting mechanisms underlying EC carcinogenesis and designing specific treatments for patients with EC, particularly the immunotherapy.

• #77 Gene function analysis and underlying mechanism of esophagus cancer based on microarray gene expression profiling | Oncotarget

  https://www.oncotarget.com/article/22160/text/

  Our results suggested that EC progression was strongly associated with (1) cell proliferation, survival, invasion, metastasis and angiogenesis (MAPK signaling pathway, cell cycle, wnt signaling pathway, VEGF-signaling pathway, MMP1, SPP1, COL11A1), (2) cell adhesion (focal adhesion, adhesion junction, calcium signaling pathway, PTK2), (3) the imbalance of oncogene and cancer suppressor gene (p53 signaling pathway, pathway in cancer, MET, PLCD1) as well as (4) the participation of the immune system (IL8, CXCR7). […] Our discovery may be of vital importance for investigating the complex interacting mechanisms underlying EC carcinogenesis and designing specific treatments for patients with EC, particularly the immunotherapy.

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