The mitochondrial hinge protein, UQCRH, is a novel prognostic factor for hepatocellular carcinoma.
Alterations in mitochondrial respiration contribute to the development and progression of cancer via abnormal biogenesis, including generation of reactive oxygen species. Ubiquinol-cytochrome c reductase hinge protein (UQCRH) consists of the cytochrome bc1 complex serving respiration in mitochondria. In the present study, we analyzed UQCRH abnormalities in hepatocellular carcinoma (HCC) and its association with clinical outcomes of patients. UQCRH expression in HCC was determined via semiquantitative and quantitative real-time reverse transcriptase polymerase chain reaction of 96 surgically resected HCC tissues positive for hepatitis B virus surface antigen. UQCRH was frequently overexpressed in HCC tissues (46.8%, based on 2.1-fold cutoff). UQCRH overexpression was observed in HCCs with larger tumor size, poorer differentiation, or vascular invasion. Kaplan-Meier analysis revealed significantly shorter overall (P = 0.005) and recurrence-free survival (P = 0.027) in patients with tumors overexpressing UQCRH. The prognostic impact of UQCRH was significant in subgroups of patients divided according to the α-fetoprotein (AFP) level. The patient subgroup with higher AFP levels (≥20 ng/mL) exhibited significant differences in 5-year overall (18.5% vs. 67.9%) and recurrence-free survival rates (11.1% vs. 46.4%) between groups with and without UQCRH overexpression. In contrast, no marked survival differences were observed between subgroups with lower AFP levels (<20 ng/mL). Multivariate analysis defined UQCRH as an independent poor prognostic factor. Conclusively, our results indicate that UQCRH overexpression is correlated with poor outcomes of HCC patients. Furthermore, in patients grouped as high risk based on elevated AFP, lack of UQCRH overexpression could be a useful indicator for clinical treatment.
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.|Department of Pathology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Eun-Ran
ER
Park
Department of Surgery, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Sang-Bum
SB
Kim
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Jee-San
http://orcid.org/0000-0002-3620-9485
JS
Lee
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Yang-Hyun
YH
Kim
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Dong-Hyoung
DH
Lee
Department of Surgery, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Eung-Ho
EH
Cho
Department of Pathology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Sun-Hoo
SH
Park
Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Chul Ju
CJ
Han
Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea.
Bu-Yeo
BY
Kim
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Dong Wook
DW
Choi
Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Seoul, Korea.
Young Do
YD
Yoo
Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Seoul, Korea.
Ami
A
Yu
Department of Statistics, Korea University, Seoul, Korea.
Jae Won
JW
Lee
Department of Pathology, Seoul National University School of Medicine, Seoul, Korea.
Ja June
JJ
Jang
Department of Pathology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Young Nyun
YN
Park
Department of Surgery, Seoul National University School of Medicine, Seoul, Korea.
Kyung-Suk
KS
Suh
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.|Department of Biotechnology, College of Natural Science, Seoul Women's University, Seoul, Korea.
Kee-Ho
KH
Lee
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000821:virology; D014450:Electron Transport Complex III / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D047368:Tumor Burden; D015854:Up-Regulation
D006514:Hepatitis B Surface Antigens; C039762:UQCRH protein, human; D014450:Electron Transport Complex III

AFP
; Mitochondria; Prognosis; UQCRH overexpression; hepatocellular carcinoma