An endogenous DNA adduct as a prognostic biomarker for hepatocarcinogenesis and its prevention by Theaphenon E in mice

Autor: Marcin Dyba, Heidi Coia, Fung-Lung Chung, Shana Silverstein, Monika Aggarwal, Justine N. McCutcheon, Giuseppe Giaccone, Aiwu Ruth He, Bhaskar Kallakury, Jishen Pan, Angela Bai, Ying Fu, Yu-Wen Zhang, Raghu G. Nath, Jiji Jiang, Hongkun Wang
Rok vydání: 2017
Předmět:
Zdroj: Hepatology. 67:159-170
ISSN: 1527-3350
0270-9139
DOI: 10.1002/hep.29380
Popis: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, mainly because of its poor prognosis. A valid mechanism-based prognostic biomarker is urgently needed. γ-hydroxy-1,N2-propanodeoxyguanosine (γ-OHPdG) is an endogenously formed mutagenic DNA adduct derived from lipid peroxidation (LPO). We examined the relationship of γ-OHPdG with hepatocarcinogenesis in two animal models and its potential role as a prognostic biomarker for recurrence in HCC patients. Bioassays were conducted in the Xeroderma pigmentosum group A knockout mice (Xpa-/-), and the diethylnitrosamine (DEN)-injected mice, both prone to HCC development. γ-OHPdG levels in the livers of these animals were determined. The effects of antioxidant treatments on γ-OHPdG and hepatocarcinogenesis were examined. Using two independent sets of HCC specimens from patients, we examined the relationship between γ-OHPdG and survival or recurrence-free survival. γ-OHPdG levels in liver DNA showed an age-dependent increase and consistently correlated with HCC development in all three animal models. Theaphenon E treatment significantly decreased γ-OHPdG levels in the liver DNA of Xpa-/- mice, and remarkably reduced HCC incidence in these mice to 14% from 100% in the controls. It also effectively inhibited HCC development in the DEN-injected mice. Using clinical samples from two groups of patients, our study revealed that higher levels of γ-OHPdG are strongly associated with low survival (p
Databáze: OpenAIRE
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