Building and validating a cervical cancer prognosis risk model based on alternative splicing data
Objective Based on the cancer genome atlas(TCGA)database,variable shear(AS)events and related genes of cervical cancer were analyzed,and the relationship between AS events and patients'prognosis and survival was dis-cussed,and the prognostic risk model of AS events was constructed and verified.Methods Download cervical cancer related AS data,RNA sequencing(RNA-Seq)data and clinical sample data from TCGA SpliceSeq and TCGA database.The R soft-ware was used to screen and sort out 94 valid samples for analysis,and 7 types of AS events in the samples were studied.Sin-gle-factor Cox regression analysis was used to screen for AS events related to cervical cancer survival.Least absolute shrink-age and selection operator(LASSO)regression analysis was used to construct an AS-based prognostic risk model,and the risk score was calculated to divide the patients into high risk group and low risk group.Survival curve and receiver operator char-acteristic(ROC)curve were drawn to evaluate the model effectiveness.Independent prognostic analysis was performed by Cox regression analysis with single and multiple factors.Combining RNA-Seq data,the regulatory network of AS events and shear factors(SF)was constructed.Results Among all AS events in cervical cancer,the most common AS events are exon skip(ES)and alternative promoter(AP).Among all the AS events associated with the prognosis of cervical cancer,ES type is the most common and mutually exclusive exons(ME)type is the least,and most AS events are significantly associated with sur-vival.LASSO regression analysis and Cox regression analysis showed that FCF1 and cytoplasmic linker protein 1(CLIP1)variable donor sites,plasma protease C1 inhibitor(SERPING1)and optic atrophin 3(OPA3)variable promoters,NADH dehydrogenase Ⅰ alpha subcomplex 4(NDUFA3),NHL repeat-containing protein 3(NHLRC3),mannosidase alpha class 2A member 2(MAN2A2)exon hopping were all AS events highly correlated with the prognosis of cervical cancer patients.Kap-lan-Meier survival analysis showed that the survival of patients in the high-risk group was significantly lower than that in the low-risk group.ROC curve indicated that the prognostic risk model of cervical cancer had good prediction,and AUC values were all＞0.9.The risk score of the prognostic model is an independent prognostic factor for cervical cancer.The regulatory network of AS events and SF showed that a total of 19 SFS were highly involved in 372 AS events,among which poly-cytosine binding proteins(PCBP),small nuclear ribonucleoproteins 35(SNRNP35),ring finger protein 40(RNF40)and small nuclear ribonucleoprotein A(SNRPA)were associated with multiple AS events.Conclusion AS events are closely re-lated to the occurrence,development and prognosis of cervical cancer.The prognostic risk model established based on AS can effectively predict the survival time and survival status of cervical cancer patients,and has high predictive value.Prognostic AS gene and SF can be used as potential molecular markers for cervical cancer treatment.
cervical canceralternative splicingsplicing factorTCGA databaseprognostic risk model
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