A Prognostic Model for Prostate Cancer Patients Based on Two DNA Damage Response Mutation-Related Immune Genes.

ABSTRACT

Background: DNA damage response (DDR) mutation-related genes and composition of immune cells are core factors affecting the effectiveness of immune checkpoint inhibitor therapy. The aim of this study is to combine DDR with immune-related genes to screen the prognostic signature for prostate cancer (PCa). Methods: Gene expression profile and somatic mutation were downloaded from The Cancer Genome Atlas (TCGA). DDR-related genes were obtained from published study. After identification of prognostic-related DDR genes, samples were divided into mutation and nonmutation groups. Differentially expressed genes between these two groups were screened, followed by selection of immune-related DDR genes. Univariate and multivariate Cox analyses were performed to screen genes for constructing prognostic model. Nomogram model was also developed. The expression level of signature was detected by quantitative real-time PCR (qPCR). Results: Two genes (MYBBP1A and PCDHA9) were screened to construct the prognostic model, and it showed good risk prediction of PCa prognosis. Survival analysis showed that patients in high-risk group had worse overall survival than those in low-risk group. Cox analyses indicated that risk score could be used as an independent prognostic factor for PCa. qPCR results indicated that MYBBP1A was upregulated, whereas PCDHA9 was downregulated in PCa cell lines. Conclusions: A prognostic model based on DDR mutation-related genes for PCa was established, which serves as an effective tool for prognostic differentiation in patients with PCa.