Construction and validation of risk models for apoptosis-related genes in cervical cancer

JIANG Qian; GUAN Yongge; HUANG Cailian; LIANG Zhuoyan

doi:10.3969/j.issn.1009-0460.2025.06.004

Abstract：Objective To explore the role of Anoikis in the occurrence and development of cervical cancer,construct a prognostic prediction model based on anoikis-related genes(ARGs),and analyze its relationship with the immune microenvironment of cervical cancer.Methods The gene expression profiles and clinical data of 304 cases of cervical cancer(CESC)were downloaded from the TCGA database.ARGs were screened by combining GeneCards and Harmonizome.Differentially expressed ARGs were identified by limma package and Wilcoxon test(FDR<0.05,|logFC|>1).The univariate Cox proportional hazards regression model was used to screen genes related to the prognosis of CESC.ConsensusClusterPlus was adopted for consistency clustering and typing(k=3);The risk model was constructed based on LASSO-Cox regression,and the expression of differential genes was verified through the GSE9750 and GSE63514 datasets.A nomogram model was constructed in combination with clinicopathological characteristics.Immune infiltration was evaluated by CIBERSORTx and ESTIMATE,and the expression relationship between ARGs and immune checkpoint genes(such as PD-L1,CTLA4,etc.)was analyzed by Spearman correlation analysis.Results A total of 19 ARGs related to the prognosis of CESC were identified(P<0.05),among which BCL2,EDA2R,FASN,ITGA8,and NRP1 constituted the risk model.The overall survival period of the high-risk group was significantly shortened(HR=2.41,95%CI=1.56-3.73,P<0.001),and the risk score was an independent prognostic factor(P=0.003).Secondary clustering analysis based on model genes showed that the risk score of the Cluster2 subtype was significantly increased and the prognosis was worse(P<0.001).The AUC of the nomogram for predicting the 3-year survival rate was 0.82(calibration curve C-index=0.75).Conclusion The nomogram model composed of antectic apoptosis-related genes such as BCL2 and EDA2R can effectively predict the prognosis of cervical cancer.Its mechanism may be related to the regulation of the tumor immune microenvironment and can provide potential targets for individualized treatment of cervical cancer.