Biomarkers Identification Of Potential Carcinogenic Risk Factors For ACEI Antihypertensive Drugs

Objective:Hypertension is the most common chronic noncommunicable disease and one of the leading causes of death from cardiovascular disease around the world.In clinical practice,antihypertensive drug therapy is the most commonly treatment,but in recent years,antihypertensive drug safety problems occur frequently.From the perspective of multi-omics,this research studied the first-line anti-hypertensive drugs of ACEI class,and matched the expression patterns with the specific genes of 33 cancer types,explored the potential carcinogenic risk factors and screened the related biomarkers,providing a reference for the drug treatment of hypertension from the multi-omics perspective.Methods:The proper gene expression profile data of ACEI antihypertensive drugs was obtained through GEO,ArrayExpress and other gene expression databases.Bioinformatics methods was used to identify differentially expressed genes(DEGs)and functional enrichment and pathway analysis.In addition to the target data of ACEI drugs obtained from Drugbank,PharmGKB,KEGG Drug databases,the target genes of ACEI antihypertensive drugs were obtained comprehensively.Then,the differential expression analysis of ACEI-DEGs was carried out in UALCAN database to study its expression level in 33 kinds of cancers,and the genes with significant difference and consistent with ACEI-DEGs expression pattern(up or down)were screened.The protein interaction network analysis was carried out on each gene set to screen Hub gene(protein).The survival time clinical data of the relevant cancer samples were obtained from TCGA,and the Hub gene(protein)was analyzed for survival.Finally,the genes whose gene expression was consistent with the laws reflected by the survival curve were selected as key genes and used as biomarkers of ACEI antihypertensive drugs and potential risk factors of various cancers.Results:Gene expression profile data GSE83095 of ACEI antihypertensive drugs were obtained from GEO and analyzed for differentially expressed genes.A total of 395 differentially expressed genes were obtained,including 261 up-regulated genes and 134down-regulated genes.Eleven ACEI drug target data were obtained from comprehensivedrug databases Drugbank,PharmGKB and KEGG Drug,and the related target gene set of ACEI antihypertensive drugs was obtained,including 405 genes.According to the analysis results of UALCAN database,there are 21 kinds of cancers with consistent genes.After protein interaction network analysis and TCGA survival analysis,10 genes including TRMT112,GGCT,PSMA1,FRK,IP6K3,RPS8,EMG1,EIF4A3,EIF3 M and RAN were finally screened out to have potential association with 7 cancers including BLCA,BRCA,HNSC,KIRC,KIRP,LIHC and LUAD.Conclusion:This research analyzed the ACEI antihypertensive drugs safety from the perspective of multi-omics,and found ACEI anti-hypertensive drugs had potential relationship with 15 cancer types in carcinogenic risk.The 10 biomarkers of carcinogenic risk factors obtained in this research may provide certain guiding significance for the development of clinical drug treatment plans for hypertension in the future.