Predictive Value of the TP53 p.G245S Mutation Frequency for the Short-Term Recurrence of Hepatocellular Carcinoma as Detected by Pyrophosphate Sequencing

内科学 比例危险模型 肝细胞癌 医学 肿瘤科 突变 胃肠病学 接收机工作特性 多元分析 突变频率 单变量分析 生物 遗传学 基因
作者
Xi Yu,Shuqi Mao,Yuying Shan,Yi‐Hsiang Huang,Shengdong Wu,Caide Lu
出处
期刊:Genetic Testing and Molecular Biomarkers [Mary Ann Liebert, Inc.]
卷期号:26 (10): 476-484
标识
DOI:10.1089/gtmb.2022.0032
摘要

Aims: We explored the relationship between the mutation at the p.G245S site in TP53 and the short-term recurrence of hepatocellular carcinoma (HCC). Materials and Methods: 101 HCC patients were included in this study. The TP53 p.G245S mutation frequency spectrum was examined by direct sequencing of genomic DNA from tissue specimens of HCC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the independent prognostic factors of tumor recurrence. ROC curve analysis was applied to determine the cut-off value for the p.G245S mutation frequency and to verify the predictive ability of the Cox model compared with single risk factor indices. Results: A multivariate Cox regression analysis showed that TP53 p.G245S mutation frequency (HR = 1.231, 95% CI: 1.006–1.505, p = 0.043), AFP (HR = 2.432, 95% CI: 1.297–4.561, p = 0.006), MTM (HR = 2.656, 95% CI: 0.930–7.583, p = 0.068), and PVTT (HR = 14.297, 95% CI: 3.085–66.243, p = 0.001) were independent prognostic factors for short-term recurrence. The cut-off value for the TP53 p.G245S mutation frequency (18.5%) was determined by ROC analysis. A predictive model integrating the TP53 p.G245S mutation frequency with PVTT, MTM, and AFP values appears to an excellent predictive indicator of short-term recurrence in HCC patients (AUC = 0.849, 95% CI = 0.748–0.950, p = 0.000001). Survival analysis indicated that the probability of short-term recurrence-free survival was significantly different among different TP53 p.G245S mutation frequency, MTM, PVTT, and AFP risk groups (p < 0.05). Conclusion: The mutation frequency of the p.G245S site is a novel prognostic risk factor for the short-term recurrence of HCC.

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