Influence of expression and methylation of DNA damage repair genes on survival prognosis of hepatocellular carcinoma and establishment of a risk prognostic scoring model
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.
万方数据
维普
