Construction and experimental verification of the combined prognostic signature of pyroptosis, apoptosis and necroptosis for cervical cancer

Objective: To construct a prognostic signature of cervical cancer(CC)associated with combined programmed cell death(PCD).Methods: The differentially expressed genes(DEGs)of pyroptosis(P), apoptosis(A)and necroptosis (N) in CC were screened respectively.DEGs related to combined PCD (PANDEGs) were obtained after intersection.Univariate, LASSO and stepwise multivariate Cox regression models were used to screen out PANDEGs related to prognosis and a prognostic signature was established.CC patients were divided into high and low risk groups according to the median risk score.The survival curve was drawn to verify the effect of the signature on the prognosis of patients.The expression differences of prognostic genes in tissue samples were confirmed by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).In addition, a nomogram was drawn and functional enrichment analysis related to the model was performed.Results: Finally, four key genes with prognostic value(NOD1, TNF, BCL2 and NDRG2)were screened out from the 65 PANDEGs.Kaplan-Meier analysis showed that the overall survival(OS)of the low-risk group was significantly longer than that of the high-risk group.The nomogram showed that the predicted survival was in good agreement with the actual observation.The expression levels of NOD1, TNF, BCL2 and NDRG2 between CC tissues and normal cervical tissues were significantly different (P＜0.05).Conclusion: This prognostic signature can be used as an effective tool to predict the prognosis of CC patients.NOD1, TNF, BCL2 and NDRG2 may become new therapeutic targets for CC.