Establishment of a prognostic model for predicting short-term disease-free survival in cases of hepatitis B-related hepatocellular carcinoma with the TP53 249Ser mutation in southern China

建立预测中国南方地区TP53 249Ser突变型乙型肝炎相关肝细胞癌患者短期无病生存期的预后模型

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Abstract

BACKGROUND: Hepatitis B virus (HBV) infection and dietary aflatoxin exposure are two major and synergistic carcinogenic factors of hepatocellular carcinoma (HCC) in southern China. Mutation of the TP53 gene at codon 249 (TP53 249Ser) is recognized as a fingerprint of aflatoxin B1 (AFB1) exposure. METHODS: A total of 485 HCC patients positive for serum hepatitis B surface antigen were enrolled. The clinicopathological information and survival time were collected. TP53 249Ser mutations in HCC were detected by Sanger DNA sequencing after PCR amplification. Immunohistochemical staining was used to evaluate TP53 expression. Propensity score matching (PSM) and Cox proportional hazards regression (CPHR) were conducted to identify independent risk factors for prognosis that were incorporated into the nomogram. Univariate logistic regression analysis was used to compare differences in clinical factors between the TP53 249Ser mutation group and the non-mutation group. A Kaplan-Meier plot, univariate and multivariate Cox proportional hazards models were used to assess the association between clinicopathological characteristics and survival outcomes. RESULTS: After PSM, a total of 322 cases were included in the analysis of clinical prognosis. Results of CPHR showed that the mutation group had a relatively higher risk of tumor recurrence within 2 years after undergoing hepatectomy (P=0.039, HR =1.47, 95% CI: 1.02-2.18). The prognostic model performed better in terms of 2-year DFS prediction than BCLC stage. Patients who had a nomogram score of more than 160 were considered to have a higher risk of recurrence within 2 years. CONCLUSIONS: Our study found that the TP53 249Ser mutation may be a high risk factor of HBV-related HCC recurrence in the short term. And we initially established a nomogram scoring system for predicting 2-year recurrence in HBV-related HCC patients in southern China.

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