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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2007

01-03-2007

Predictive Power of Biomarkers of Oxidative Stress and Inflammation in Patients with Hepatitis C Virus-Associated Hepatocellular Carcinoma

Authors: Akira Maki, Hiroshi Kono, Mayetri Gupta, Masami Asakawa, Tetsuya Suzuki, Masanori Matsuda, Hideki Fujii, Ivan Rusyn

Published in: Annals of Surgical Oncology | Issue 3/2007

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Abstract

Background

This study evaluated the relationship between inflammation, intra-hepatic oxidative stress, oxidative DNA damage and the progression of liver carcinogenesis in hepatitis C virus (HCV)-infected humans.

Methods

Non-cancerous liver tissues were collected from 30 patients with an HCV-associated solitary hepatocellular carcinoma (HCC) who received curative tumor removal. After surgery, the patients were followed at monthly intervals at the outpatient clinic. Distribution of the inflammatory cells (CD68+), the number of 8-hydroxydeoxyguanosine (8-OHdG) DNA adducts and 4-hydroxynonenal (HNE) protein adducts and the expression of apurinic/apyrimidinic endonuclease (APE) were determined by immunohistochemical analysis in serial liver sections from tumor-free parenchyma at the surgical margin around the tumor.

Results

Significant positive correlations were observed between the number of CD68+ cells, the amount of HNE protein adducts, and the number of 8-OHdG adducts in liver tissue of patients with HCC and HCV. The cumulative disease-free survival was significantly shorter in patients with the highest percentage of 8-OHdG-positive hepatocytes. Using a Cox proportional hazard model, 8-OHdG, HNE and CD68 were determined to be good biomarkers for predicting disease-free survival in patients with HCC and HCV.

Conclusions

These results support the hypothesis that HCV-induced inflammation causes oxidative DNA damage and promotes hepatocarcinogenesis which directly affects the clinical outcome. Since patients with greater intra-hepatic oxidative stress had a higher incidence of HCC recurrence, we suggest that oxidative stress biomarkers could potentially be used as a useful clinical diagnostic tool to predict the duration of disease-free survival in patients with HCV-associated HCC.
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Metadata
Title
Predictive Power of Biomarkers of Oxidative Stress and Inflammation in Patients with Hepatitis C Virus-Associated Hepatocellular Carcinoma
Authors
Akira Maki
Hiroshi Kono
Mayetri Gupta
Masami Asakawa
Tetsuya Suzuki
Masanori Matsuda
Hideki Fujii
Ivan Rusyn
Publication date
01-03-2007
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 3/2007
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-006-9049-1

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