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.
Department of Pathology, The Affiliated Provincial Hospital of Shandong First Medical University, Jinan, Shandong Province, P.R. China.
Aging (Albany NY). 2023 Jul 28;15(14):7258-7277. doi: 10.18632/aging.204910.
Chronic inflammation and lipid peroxidation (LPO) are associated with the pathogenesis of hepatocellular carcinoma (HCC), and γ-hydroxy-1, N-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.
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.
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.
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.
慢性炎症和脂质过氧化（LPO）与肝细胞癌（HCC）的发病机制有关，γ-羟基-1，N-丙酰基脱氧鸟苷（γ-OHPdG）是一种源自 LPO 的促突变 DNA 加合物。本研究旨在探讨 γ-OHPdG 与肝癌发生发展的关系。
从 228 例原发性 HCC 标本和 46 例肝硬化标本中获得患者的 HCC 组织和癌旁组织、肝硬化组织。通过门诊和电话随访对患者术后进行随访。采用免疫组化分析检测癌组织及癌旁组织、肝硬化组织中γ-OHPdG 的水平。
癌组织中 γ-OHPdG 水平明显高于癌旁组织（P < 0.001），也高于肝硬化组织。随着肿瘤大小、组织学分级、MVI 分级、T 分期、Ki67 阳性细胞百分比和 HCC 进展，癌组织中 γ-OHPdG 水平呈逐渐升高趋势。此外，预后分析显示，癌组织中较高的 γ-OHPdG 水平与总生存期（P < 0.001）、肝内无复发生存率（P < 0.001）和远处无转移生存率（P < 0.05）显著降低密切相关。虽然没有统计学意义，但肝硬化进展为 HCC 的患者中 γ-OHPdG 水平呈上升趋势，而 γ-OHPdG 水平与肝硬化进展为 HCC 的时间呈负相关。
这些结果表明，γ-OHPdG 是预测 HCC 患者预后的生物标志物，可能是预测肝硬化患者 HCC 的前瞻性指标。
