title: Bi-directional roles of IRF-1 on autophagy diminish its prognostic value as compared with Ki67 in liver transplantation for hepatocellular carcinoma.
abstract: The prognostic values of IRF-1 and Ki-67 for liver transplantation (LT) of hepatocellular carcinoma (HCC) were investigated, as well as the mechanisms of IRF-1 in tumor suppression. Adult orthotropic liver transplantation cases (N = 127) were involved in the analysis. A significant decreased recurrence free survival (RFS) was found in the Ki-67 positive groups. Ki-67, tumor microemboli, the Milan and UCSF criteria were found to be independent risk factors for RFS. In LT for HCC beyond the Milan criteria, a significant decrease in RFS was found in the IRF-1 negative groups. In SK-Hep1 cells, an increase in apoptosis and decrease in autophagy were observed after IFN-γ stimulation, which was accompanied with increasing IRF-1 levels. When IRF-1 siRNA or a caspase inhibitor were used, reductions in LC3-II were diminished or disappeared after IFN-γ stimulation, suggesting that IFN-γ inhibited autophagy via IRF-1 expression and caspase activation. However, after IRF-1 siRNA was introduced, a reduction in LC3-II was found. Thus basic expression of IRF-1 was also necessary for autophagy. IRF-1 may be used as a potential target for HCC treatment based on its capacity to affect apoptosis and autophagy. Ki-67 shows great promise for the prediction of HCC recurrence in LT and can be used as an aid in the selection of LT candidates.
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin, P. R. China.|Department of Transplantation, Tianjin First Central Hospital, Tianjin, P. R. China.|Tianjin Key Laboratory of Organ Transplantation, Tianjin, P. R. China.
authors.forename: Hai-Ming
authors.initials: HM
authors.lastname: Zhang
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin, P. R. China.|Tianjin Key Laboratory of Organ Transplantation, Tianjin, P. R. China.|Laboratory of Immunology and Inflammation, Tianjin Medical University, Tianjin, P. R. China.
authors.forename: Shi-Peng
authors.initials: SP
authors.lastname: Li
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin, P. R. China.|Tianjin Key Laboratory of Organ Transplantation, Tianjin, P. R. China.|Laboratory of Immunology and Inflammation, Tianjin Medical University, Tianjin, P. R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin, P. R. China.|Tianjin Key Laboratory of Organ Transplantation, Tianjin, P. R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin, P. R. China.|Tianjin Key Laboratory of Organ Transplantation, Tianjin, P. R. China.
authors.forename: Jin-Dan
authors.initials: JD
authors.lastname: He
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin, P. R. China.|Laboratory of Immunology and Inflammation, Tianjin Medical University, Tianjin, P. R. China.
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Xu
authors.affiliation: Laboratory of Immunology and Inflammation, Tianjin Medical University, Tianjin, P. R. China.
authors.forename: Rong-Xin
authors.initials: RX
authors.lastname: Zhang
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin, P. R. China.|Department of Transplantation, Tianjin First Central Hospital, Tianjin, P. R. China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Beijing Friendship Hospital, China Capital Medical University, Beijing, P. R. China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Zhu
authors.affiliation: First Central Clinical College, Tianjin Medical University, Tianjin, P. R. China.|Department of Transplantation, Tianjin First Central Hospital, Tianjin, P. R. China.|Tianjin Key Laboratory of Organ Transplantation, Tianjin, P. R. China.
authors.forename: Zhong-Yang
authors.initials: ZY
authors.lastname: Shen
mesh_terms: D001343:Autophagy / Q000502:physiology; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D016898:Interferon-alpha / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000379:methods*; D008875:Middle Aged; D011379:Prognosis; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha; D019394:Ki-67 Antigen
keywords: HCC; IRF-1; Ki-67; autophagy; liver transplantation