A Robust Prognostic Gene Signature Based On ERNA-driven Genes In Prostate Cancer

Objective:Prostate cancer(PCa)is the second most common malignancy in men,but its oncogenic mechanisms remain unclear.Our study aimed to explore the effect of enhancer RNAs(e RNAs)on PCa occurrence and to identify possible PCa biomarkers.Methods:By the database from The Cancer Genome Atlas(TCGA),we conducted the preliminary screening of e RNAs and target genes significantly related to the prognosis of patients with PCa through bootstrapping,the Kaplan–Meier(KM)survival analysis,Pearson correlation coefficient analysis,and least absolute shrinkage and selection operator(LASSO).Then,we established a risk score model of PCa and validated this risk score model in three other validation cohorts.Moreover,we explored the mechanism of the effect of e RNAs on the occurrence and development of PCa through functional analysis.In addition,we also analyzed two drugs sensitivity of PCa on the Genomics of Drug Sensitivity in Cancer(GDSC)and potential therapeutic agents through Connectivity Map(CMAP).In total,835 prostate samples were included in our work.Results:We screened three eRNAs-driven genes(MAPK15,ZNF467 and MC1R)associated with the prognosis of PCa and established a prognostic risk model in relation to the disease-free survival(DFS).The risk model performed well in both the training and validation cohorts.Moreover,we found that the genes included in the gene signature were significantly enriched in immune cell infiltration and gene mutation.Through differential analysis,we found that there were significant differences in tumor microenvironment(TME),immune cells,DNA mutation,tumor mutational burden(TMB),and microsatellite instability(MSI)between the high-and low-risk groups.Through drug sensitivity analysis,we found significant differences in IC50 in the high-and low-groups.Ten possible small molecule compounds for the treatment of PCa were screened by CMAP.Conclusion:In this study,three target genes which were significantly associated with DFS in prostate cancer patients were identified and a robust prognostic model was established.In addition,the mechanism of e RNAs’ influence on the progression of prostate cancer was tentatively explored.