Complex IV subunit 1 defect predicts postoperative survival in hepatocellular carcinoma

Mitochondrial oxidative phosphorylation (OXPHOS) is responsible for adenosine triphosphate synthesis and OXPHOS deficiency plays a significant role in tumorigenesis. The defects of mitochondrial-encoded OXPHOS subunits have been found in normal and cirrhotic liver, however their contributions in hepatocellular carcinoma (HCC) are not clear. The present study aimed to examine these defects in resected HCC tissues. In total, 102 human HCC tissues were collected from patients undergoing curative resection, and immunohistochemical staining was performed to assess tissue expression of complex I subunit 6, complex III subunit 3, complex IV subunit 1 (CIV-1) and complex V subunit 6. Cox proportional hazard model analysis was performed, including all clinicopathological factors, to postoperatively estimate the overall survival rate. The results showed that the majority of HCC tissues contained various degrees of expression defects for OXPHOS subunits. Among these, the major CIV-1 defect (expression defect area of >25% of the examined area) (P<0.001) and early distant metastasis (P<0.001) were independently associated with the overall survival rate. Kaplan-Meier analysis also demonstrated that the major CIV-1 defect was significantly associated with a poor overall survival rate (log-rank, P=0.002). The findings in the present study clearly indicate that the major CIV-1 expression defect may serve as an independent negative prognostic factor in HCC patients following curative resection.