title: Role of interleukin 1 beta in esophageal squamous cell carcinoma.
abstract: Interleukin (IL)-1 beta has been reported to be a marker of shorter survival in gastric and colorectal adenocarcinoma. In the present study, we examined the potential role and prognostic value of IL-1 beta in esophageal squamous cell carcinoma (SCC). Human esophageal SCC cell line, CE81T, was selected for cellular and animal experiments, in which biological changes after experimental manipulation of IL-1 beta signaling were explored, including tumor growth, invasion capacity, and the sensitivity to treatment. Moreover, 147 esophageal SCC samples were analyzed using immunohistochemical staining to correlate the expression of IL-1 beta with clinical outcome. Our data revealed that IL-1 beta was significantly overexpressed both at mRNA and protein levels in cancer specimens compared to nonmalignant tissues. When IL-1 beta signaling was blocked, tumor growth, invasion ability, and treatment resistance were attenuated. Activation of NF-kappa B, increase of E2-EPF ubiquitin carrier protein and subsequent epithelial-mesenchymal transition might be the underlying mechanisms of the more aggressive tumor growth in IL-1 beta-positive esophageal cancer. The immunochemistry findings indicate that positivity staining of IL-1 beta correlated significantly with higher clinical stage, lower response rate to concurrent chemoradiotherapy (CCRT), and higher recurrence rate after curative treatment. Moreover, IL-1 beta was a significant predictor of survival in patients undergoing surgical intervention or definite CCRT. In conclusion, IL-1 beta is significantly linked to poor prognosis for patients with esophageal cancer and may be a promising molecular target for therapeutic intervention for esophageal SCC.
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital at Chia-Yi, Chia-Yi, Taiwan.
authors.forename: Miao-Fen
authors.initials: MF
authors.lastname: Chen
authors.forename: Ming-Shian
authors.initials: MS
authors.lastname: Lu
authors.forename: Ping-Tsung
authors.initials: PT
authors.lastname: Chen
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Chen
authors.forename: Paul-Yang
authors.initials: PY
authors.lastname: Lin
authors.forename: Kuan-Der
authors.initials: KD
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002109:Caffeic Acids / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D011379:Prognosis; D011836:Radiation Tolerance / Q000235:genetics; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D002109:Caffeic Acids; D053583:Interleukin-1beta; D016328:NF-kappa B; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D002945:Cisplatin