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.
Highlights
Given the shortage of liver donors, effective use of liver donations represents an important medical and ethical issue
In SK-Hep1 cells, an increase in apoptosis and decrease in autophagy were observed after IFN-γ stimulation, which was accompanied with increasing Interferon regulatory factor 1 (IRF-1) levels
Results obtained using Western Blot tests demonstrated that levels of LC3-II and Beclin1 were decreased in the SK-Hep1 cells stimulated with IFN-γ as compared with the control group (Figure 4A)
Summary
Given the shortage of liver donors, effective use of liver donations represents an important medical and ethical issue. As one approach to address this problem, a number of requirements for an accurate evaluation regarding the outcome of liver transplantation (LT) for hepatocellular carcinoma (HCC) have been presented. LT for HCC has a distinct recurrence pattern from that of liver resection. Even a recurrent lesion within a liver graft can result from an extrahepatic metastasis. While a number of biomarkers, such as CK, CK19, GPC3, AFP, VEGF, EGFR, ERCC1, RRM1, TYMS, BRCA1, p53, VIM and Ki-67 are currently available for clinical assessment of tumor behavior, their prognostic value for LT of HCC is not clear. Upstream regulatory factors require further investigation for their effectiveness as markers and understanding of mechanisms of action
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