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.
Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
Puo-Hsien
PH
LE
Department of Pathology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
Shih-Chiang
SC
Huang
Department of Neurology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
Siew-Na
SN
Lim
Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
Chang-Hua
CH
Chou
Department of General Surgery, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
Ta-Sen
TS
Yeh
Department of Pathology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
Tse-Ching
TC
Chen
Department of Nephrology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
Tzung-Hai
TH
Yen
Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
Ming-Yao
MY
Su
Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
Cheng-Tang
CT
Chiu
Liver Research Center, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
Chau-Ting
CT
Yeh
Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
Wey-Ran
WR
Lin
ATP synthase; NADH dehydrogenase; cytochrome b; cytochrome c oxidase