Identification of a DNA Repair Gene Signature and Establishment of a Prognostic Nomogram Predicting Biochemical-Recurrence-Free Survival of Prostate Cancer

摘要

Background: The incidence of prostate cancer (PCa) is high and increasing worldwide. The prognosis of PCa is relatively good, but it is important to identify the patients with a high risk of biochemical recurrence (BCR) so that additional treatment could be applied. Method: Level 3 mRNA expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) to serve as training data. The GSE84042 dataset was used as a validation set. Univariate Cox, lasso Cox, and stepwise multivariate Cox regression were applied to identify a DNA repair gene (DRG) signature. The performance of the DRG signature was assessed based on Kaplan–Meier curve, receiver operating characteristic (ROC), and Harrell's concordance index (C-index). Furtherly, a prognostic nomogram was established and evaluated likewise. Results: A novel four DRG signature was established to predict BCR of PCa, which included POLM, NUDT15, AEN, and HELQ. The ROC and C index presented good performance in both training dataset and validation dataset. The patients were stratified by the signature into high- and low-risk groups with distinct BCR survival. Multivariate Cox analysis revealed that the DRG signature is an independent prognostic factor for PCa. Also, the DRG signature high-risk was related to a higher homologous recombination deficiency (HRD) score. The nomogram, incorporating the DRG signature and clinicopathological parameters, was able to predict the BCR with high efficiency and showed superior performance compared to the model that consisted of only clinicopathological parameters. Conclusion: Our study identified a DRG signature and established a prognostic nomogram, which were reliable in predicting the BCR of PTC. This model could help with individualized treatment and medical decision making.