title: Prognostic and Therapeutic Values of Tumor Necrosis Factor-Alpha in Hepatocellular Carcinoma.
abstract: BACKGROUND Hepatocellular carcinoma (HCC) causes many deaths worldwide every year, especially in Asia. It is characterized by high malignancy, recurrence, and short survival time. Inflammation is closely related to the initiation and development of HCC. Tumor necrosis factor-α (TNF-α), an essential inflammatory mediator, has been studied as a potential therapy target in many cancers. However, its potential role in HCC diagnosis and therapy is still unclear. MATERIAL AND METHODS In our study, we detected the TNF-α expression in both human HCC tumor tissue and HCC cell lines HepG2 and HuH7. Then, we detected the effect of anti-TNF-α treatment and it synergistic function with 5-FU in an HCC xenograft mouse model and in HCC cell lines. RESULTS Survival analysis and Cox regression analysis based on 97 HCC patients indicated that a high level of TNF-α is an independent predictor of poor survival in HCC patients. Anti-TNF-α treatment by infliximab synergizes with Fluorouracil (5-FU) by promoting apoptosis of HCC tumor cells through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) effects. CONCLUSIONS Based on these data, we conclude that anti-TNF-α treatment could be a good way to increase the effect of classic chemotherapy of HCC patients, especially for the patients who have modest response to classic chemotherapy, such as 5-FU. TNF-α could also be used as a biomarker to help in early diagnosis of HCC.
authors.affiliation: Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, China (mainland).
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Allergy and Clinical Immunology Research Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, China (mainland).
authors.forename: Jianmin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, China (mainland).
authors.forename: Xuemei
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, China (mainland).
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, China (mainland).
authors.forename: Baojun
authors.initials: B
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011379:Prognosis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D005472:Fluorouracil