Research Paper Volume 15, Issue 14 pp 7258—7277
The lipid peroxidation-derived DNA adduct γ-OHPdG as a diagnostic and prognostic biomarker in hepatocellular carcinoma
- 1 Department of Pathology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Clinical Pathology, Shandong Lung Cancer Institute, Shandong Institute of Nephrology, Jinan, Shandong Province, P.R. China
- 2 Department of Pathology, The Affiliated Provincial Hospital of Shandong First Medical University, Jinan, Shandong Province, P.R. China
- 3 Shandong Life Science and Technology Ltd., Dezhou, Shandong Province, P.R. China
- 4 University of California San Diego, San Diego, CA 92093, USA
- 5 Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC 20007, USA
Received: March 30, 2023 Accepted: June 26, 2023 Published: July 28, 2023
https://doi.org/10.18632/aging.204910How to Cite
Copyright: © 2023 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Purpose: Chronic inflammation and lipid peroxidation (LPO) are associated with the pathogenesis of hepatocellular carcinoma (HCC), and γ-hydroxy-1, N2-propanodeoxyguanosine (γ-OHPdG) is a promutagenic DNA adduct derived from LPO. This study aimed to examine the relationship between γ-OHPdG and the progression of liver carcinogenesis.
Methods: Primary HCC specimens were obtained from 228 patients and cirrhosis specimens from 46 patients. The patients were followed up with after surgery via outpatient visits and telephone calls. The levels of γ-OHPdG were determined by immunohistochemical analysis in the carcinomatous tissues together with adjacent and cirrhosis tissues.
Results: γ-OHPdG levels in the cancerous tissues were significantly higher compared to adjacent tissues (P < 0.001) and also higher than the ones from the tissues of cirrhosis patients. Along with tumor size, histological grade, MVI grade, T stage, the percentage of ki67-positive cells and HCC progression, γ-OHPdG levels in cancerous tissues showed a gradually increasing trend. Moreover, prognostic analysis showed that higher γ-OHPdG levels in cancerous tissues were strongly correlated with lower overall survival (P < 0.001), lower intrahepatic recurrence-free survival (P < 0.001) and lower distant metastasis-free survival (P < 0.05). There was a trend, although not statistically significant, of increased levels of γ-OHPdG in cirrhosis cases that advanced to HCC, whereas γ-OHPdG levels reversely correlated with the period of time observed for cirrhosis advanced to HCC.
Conclusions: These results suggest that γ-OHPdG is a prognostic biomarker for predicting outcomes in HCC, and may serve as a prospective indicator for predicting HCC in cirrhosis patients.
Abbreviations
HCC: hepatocellular carcinoma; LPO: lipid peroxidation; γ-OHPdG: γ-hydroxy-1, N2-propanodeoxyguanosine; HBV: hepatitis B virus; HCV: hepatitis C virus; AFP: alpha fetal protein; TBIL: total bilirubin; ALT: alanine transaminase; AT: aspartate transaminase; PT: prothrombin time; FFPE: formalin-fixed paraffin embedded; IHC: immunohistochemistry; MVI: microvascular invasion; OS: overall survival; RFS: intrahepatic recurrence-free survival; MFS: distant metastasis-free survival.