Brief Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 28, 2011; 17(44): 4890-4898
Published online Nov 28, 2011. doi: 10.3748/wjg.v17.i44.4890
Serum manganese superoxide dismutase and thioredoxin are potential prognostic markers for hepatitis C virus-related hepatocellular carcinoma
Tsutomu Tamai, Hirofumi Uto, Yoichiro Takami, Kouhei Oda, Akiko Saishoji, Masashi Hashiguchi, Kotaro Kumagai, Takeshi Kure, Seiichi Mawatari, Akihiro Moriuchi, Makoto Oketani, Akio Ido, Hirohito Tsubouchi
Tsutomu Tamai, Hirofumi Uto, Yoichiro Takami, Kouhei Oda, Akiko Saishoji, Masashi Hashiguchi, Kotaro Kumagai, Takeshi Kure, Seiichi Mawatari, Akihiro Moriuchi, Makoto Oketani, Akio Ido, Hirohito Tsubouchi, Department of Digestive and Lifestyle Related Diseases, Human and Environmental Sciences, Health Research, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
Author contributions: Tamai T and Takami Y performed the majority of experiments; Uto H and Tsubouchi H were involved in editing the manuscript; Uto H, Oda K, Saishoji A, Hashiguchi M, Kumagai K, Kure T, Mawatari S, Moriuchi A, Oketani M and Ido A coordinated the collection of and provided all the human material for this work; Tamai T and Uto H designed the study and wrote the manuscript.
Supported by (in part) Grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Ministry of Health, Labour and Welfare of Japan
Correspondence to: Hirofumi Uto, MD, PhD, Department of Digestive and Lifestyle Related Diseases, Human and Environmental Sciences, Health Research, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. hirouto@m2.kufm.kagoshima-u.ac.jp
Telephone: +81-99-2755326 Fax: +81-99-2643504
Received: April 26, 2011
Revised: August 17, 2011
Accepted: October 14, 2011
Published online: November 28, 2011
Abstract

AIM: To evaluate the clinical significance of oxidative stress markers in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).

METHODS: Sixty-four consecutive patients who were admitted to Kagoshima University Medical and Dental Hospital were enrolled in this retrospective study. All patients had chronic liver disease (CLD) due to infection with HCV. Thirty patients with HCV-related HCC, 34 with HCV-related CLD without HCC (non-HCC), and 20 healthy volunteers (HVs) were enrolled. Possible associations between serum manganese superoxide dismutase (MnSOD) and thioredoxin (TRX) levels and clinical parameters or patient prognosis were analyzed over a mean follow-up period of 31.7 mo.

RESULTS: The serum MnSOD levels were significantly higher in patients with HCV-related HCC than in patients without HCC (P = 0.03) or HVs (P < 0.001). Similarly, serum TRX levels were also significantly higher in patients with HCV-related HCC than in patients without HCC (P = 0.04) or HVs (P < 0.01). However, serum levels of MnSOD and TRX were not correlated in patients with HCC. Among patients with HCC, the overall survival rate (OSR) was lower in patients with MnSOD levels ≥ 110 ng/mL than in patients with levels < 110 ng/mL (P = 0.01), and the OSR tended to be lower in patients with TRX levels < 80 ng/mL (P = 0.05). In addition, patient prognosis with HCC was poorest with serum MnSOD levels ≥ 110 ng/mL and serum TRX levels < 80 ng/mL. Furthermore, a multivariate analysis using a Cox proportional hazard model and serum levels of five factors (MnSOD, prothrombin time, serum albumin, serum α-fetoprotein (AFP), and serum des-γ-carboxy prothrombin) revealed that MnSOD levels ≥ 110 ng/mL (risk ratio: 4.12, 95% confidential interval: 1.22-13.88, P = 0.02) and AFP levels ≥ 40 ng/mL (risk ratio: 6.75; 95% confidential interval: 1.70-26.85, P < 0.01) were independent risk factors associated with a poor patient prognosis.

CONCLUSION: Serum MnSOD and TRX levels are potential clinical biomarkers that predict patient prognosis in HCV-related HCC.

Keywords: Oxidative stress, Manganese superoxide dismutase, Thioredoxin, Hepatitis C virus, Hepatocellular carcinoma