DNA损伤修复基因表达与甲基化对肝细胞癌预后的影响及风险评分模型构建

doi:10.3760/cma.j.issn.1007-1245.2024.19.011

国际医药卫生导报 ›› 2024, Vol. 30 ›› Issue (19): 3215-3222.DOI: 10.3760/cma.j.issn.1007-1245.2024.19.011

DNA损伤修复基因表达与甲基化对肝细胞癌预后的影响及风险评分模型构建

张杰王瑞平寇小妮樊晓丹边倩

陕西中医药大学附属医院肝病医院二病区，咸阳　712000

收稿日期:2024-05-31 出版日期:2024-10-01 发布日期:2024-10-17
通讯作者: 边倩，Email：calla84@163.com
基金资助:
陕西省教育厅青年创新团队建设科研技术项目（21JP032）；陕西中医药大学附属医院科研课题资助项目（2020MS010）

Influence of expression and methylation of DNA damage repair genes on survival prognosis of hepatocellular carcinoma and establishment of a risk prognostic scoring model

Zhang Jie, Wang Ruiping, Kou Xiaoni, Fan Xiaodan, Bian Qian

Zhang Jie, Wang Ruiping, Kou Xiaoni, Fan Xiaodan, Bian Qian

Received:2024-05-31 Online:2024-10-01 Published:2024-10-17
Contact: Bian Qian, Email: calla84@163.com
Supported by:
Scientific Research Technology Project for Construction of a Young Innovation Team Supported by Shaanxi Education Department (21JP032); Scientific Research Project Funded by Hospital Affiliated to Shaanxi University of Chinese Medicine (2020MS010)

摘要/Abstract

摘要：

目的　探讨DNA损伤修复基因表达与甲基化对肝细胞癌（HCC）预后的影响及风险评分模型构建。方法　研究时间为2024年1月至5月，由TCGA、GTEx、GEO数据库获得数据集，采用Kaplan-Meier生存分析探讨DNA损伤修复基因对HCC患者生存预后的影响，利用单因素与多因素COX比例风险回归分析关键DNA损伤修复基因、年龄、性别、肿瘤分期等因素对患者预后的影响，构建并验证Nomogram预测模型，采用一致性系数（C-index）评估Nomogram预测模型的预测效果；采用Lasso回归法建立HCC生存预后的风险预后评分模型。利用HPA数据库验证结果与上述分析结果一致。结果　8个差异表达DNA损伤修复基因（FEN1、RNASEH2A、MCM6、EXO1、RECQL4、MCM4、MCM3、MCM5）对HCC患者生存预后具有影响（均P<0.05）；COX回归分析结果显示，MCM6、pTNM分期对HCC总生存率（OS）具有独立影响；列线图模型显示MCM6、pTNM分期与患者生存预后相关（均P<0.05，C-index=0.677）；预后风险评分模型显示，RECQL4、EXO1和MCM6是影响HCC患者生存预后的关键基因。RECQL4、EXO1和MCM6基因启动子区甲基化水平随着HCC分级的升高而降低（均P<0.05）。结论　DNA损伤修复基因在HCC的进展过程中发挥一定作用，RECQL4、EXO1和MCM6进入HCC患者生存预后的风险预后评分模型，MCM6对HCC患者生存预后具有独立的影响。

关键词:

肝细胞癌, DNA损伤修复基因, 列线图

Abstract:

Objective　To investigate the effect of DNA damage repair gene expression and methylation on the prognosis of hepatocellular carcinoma ( HCC ) and the construction of risk scoring model. Methods　This study was from January to May 2024. The data set was obtained from the TCGA, GTEx, and GEO databases. Kaplan-Meier survival analysis was used to analyze the effect of DNA damage repair genes on the survival prognosis of the patients with HCC. Univariate and multivariate COX proportional hazards regression analyses were conducted to analyze the impact of key DNA damage repair genes, age, gender, tumor stage, and other factors on the patients' prognosis. A nomogram prediction model was constructed and validated, and the predictive effectiveness of the nomogram prediction model was constructed and verified. The concordance index (C-index) was used to evaluated the model's predictive effect. The risk prognostic scoring model for HCC survival prognosis was established using the Lasso regression analysis. The consistence of the results with the results of the above analyses was verified by the HPA database. Results　Eight differentially expressed DNA damage repair genes (FEN1, RNASEH2A, MCM6, EXO1, RECQL4, CETN2, PCNA, MCM4, MCM3, and MCM5) had impact on survival prognosis (all P<0.05). The COX regression analysis showed that the MCM6 and pTNM stage had independent effects on the overall survival rate of the patients with HCC. The nomogram model showed that MCM6 and pTNM stage were correlated with the patients' survival prognosis (both P<0.05, C-index=0.677). The prognostic risk scoring model showed that RECQL4, EXO1, and MCM6 were key genes influencing the survival prognosis of the patients with HCC. The methylation levels of RECQL4, EXO1 and MCM6 gene promoter regions decreased with the increase of HCC grade ( all P<0.05 ). Conclusions　DNA damage repair genes play a certain role in the progression of HCC. RECQL4, EXO1, and MCM6 are included in the risk prognostic scoring model for the survival prognosis of patients with HCC. MCM6 has an independent effect on the survival and prognosis of HCC patients.

Key words:

Hepatocellular carcinoma, DNA damage repair genes, Nomogram

张杰王瑞平寇小妮樊晓丹边倩.

DNA损伤修复基因表达与甲基化对肝细胞癌预后的影响及风险评分模型构建 [J]. 国际医药卫生导报, 2024, 30(19): 3215-3222.

Zhang Jie, Wang Ruiping, Kou Xiaoni, Fan Xiaodan, Bian Qian.

Influence of expression and methylation of DNA damage repair genes on survival prognosis of hepatocellular carcinoma and establishment of a risk prognostic scoring model [J]. International Medicine and Health Guidance News, 2024, 30(19): 3215-3222.

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DNA损伤修复基因表达与甲基化对肝细胞癌预后的影响及风险评分模型构建

Influence of expression and methylation of DNA damage repair genes on survival prognosis of hepatocellular carcinoma and establishment of a risk prognostic scoring model

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