Establishment of an age- and tumor microenvironment-related gene signature for survival prediction in prostate cancer.

Abstract

The incidence of prostate cancer (PCa) increases with age, and age and tumor microenvironment (TME) have important roles in the development of PCa, while the underlying mechanisms have not been fully elucidated. The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD) RNA-Seq, the Surveillance, Epidemiology, and End Results (SEER-PRAD), and ESTIMATE data were downloaded, and the clinical information of PRAD patients in our cohort was collected. The associations among age, TME, and PCa were analyzed. The age- and TME-related risk score (ATRS) of each TCGA-PRAD sample was calculated based on the identified age- and TME-related differentially expressed genes (DEGs), and the correlation of ATRS with immune-related characteristics of PCa patients was analyzed, and the ATRS-based overall survival (OS)-predicting nomogram was also established. Age was correlated with OS, PSA level, tumor stage, T stage, N stage, Gleason score, nerve invasion of PCa, and age was positively correlated with stromal, immune, and ESTIMATE scores. The compositions of immune cells of TCGA-PRAD patients altered with age. Nine age- and TME-related prognostic DEGs were identified, and the ATRS of each TCGA-PRAD patient was calculated based on the identified nine DEGs. The ATRS was associated with the expression of immune checkpoints and intratumoral cytolytic activity, and the ATRS-based nomogram performed well in predicting the outcomes of PCa patients. Age and TME had crucial roles in PCa, and the ATRS gene signature was associated with the immune-related characteristics of PCa patients, which showed good performance in predicting OS of PCa patients.