title: Serum manganese superoxide dismutase and thioredoxin are potential prognostic markers for hepatitis C virus-related hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Serum MnSOD and TRX levels are potential clinical biomarkers that predict patient prognosis in HCV-related HCC.
authors.affiliation: 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.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tamai
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uto
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Takami
authors.forename: Kouhei
authors.initials: K
authors.lastname: Oda
authors.forename: Akiko
authors.initials: A
authors.lastname: Saishoji
authors.forename: Masashi
authors.initials: M
authors.lastname: Hashiguchi
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kumagai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kure
authors.forename: Seiichi
authors.initials: S
authors.lastname: Mawatari
authors.forename: Akihiro
authors.initials: A
authors.lastname: Moriuchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Oketani
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
mesh_terms: D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000201:enzymology / Q000821:virology; D003937:Diagnosis, Differential; D005260:Female; D016174:Hepacivirus / Q000472:pathogenicity; D006526:Hepatitis C / Q000097:blood / Q000201:enzymology / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000201:enzymology / Q000821:virology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D012189:Retrospective Studies; D013482:Superoxide Dismutase / Q000097:blood*; D015996:Survival Rate; D013879:Thioredoxins / Q000097:blood*; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D011498:Protein Precursors; D000509:alpha-Fetoproteins; D013879:Thioredoxins; C008208:acarboxyprothrombin; D011516:Prothrombin; D013482:Superoxide Dismutase