Research Papers:

Bi-directional roles of IRF-1 on autophagy diminish its prognostic value as compared with Ki67 in liver transplantation for hepatocellular carcinoma

Hai-Ming Zhang, Shi-Peng Li, Yao Yu, Zhen Wang, Jin-Dan He, Yan-Jie Xu, Rong-Xin Zhang, Jian-Jun Zhang, Zhi-Jun Zhu and Zhong-Yang Shen _

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Oncotarget. 2016; 7:37979-37992. https://doi.org/10.18632/oncotarget.9365

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Hai-Ming Zhang1,2,3,*, Shi-Peng Li1,3,4,*, Yao Yu1,3,4, Zhen Wang1,3, Jin-Dan He1,3, Yan-Jie Xu1,4, Rong-Xin Zhang4, Jian-Jun Zhang1,2, Zhi-Jun Zhu5, Zhong-Yang Shen1,2,3

1First Central Clinical College, Tianjin Medical University, Tianjin, P. R. China

2Department of Transplantation, Tianjin First Central Hospital, Tianjin, P. R. China

3Tianjin Key Laboratory of Organ Transplantation, Tianjin, P. R. China

4Laboratory of Immunology and Inflammation, Tianjin Medical University, Tianjin, P. R. China

5Beijing Friendship Hospital, China Capital Medical University, Beijing, P. R. China

*These authors contributed equally to this work

Correspondence to:

Zhi-Jun Zhu, email: [email protected]

Zhong-Yang Shen, email: [email protected]

Keywords: IRF-1, Ki-67, autophagy, HCC, liver transplantation

Received: March 13, 2016     Accepted: April 27, 2016     Published: May 13, 2016


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.

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