Characterization of a Pyroptosis-Related Signature for Prognosis Prediction and Immune Microenvironment Infiltration in Prostate Cancer

Abstract

This study was aimed at constructing a pyroptosis-related signature for prostate cancer (PCa) and elucidating the prognosis and immune landscape and the sensitivity of immune checkpoint blockade (ICB) therapy in signature-define subgroups of PCa. We identified 22 differentially expressed pyroptosis-related genes in PCa from The Cancer Genome Atlas (TCGA) database. The pyroptosis-related genes could divide PCa patients into two clusters with differences in survival. Seven genes were determined to construct a signature that was confirmed by qRT-PCR to be closely associated with the biological characteristics of malignant PCa. The signature could effectively and independently predict the biochemical recurrence (BCR) of PCa, which was validated in the GSE116918 and GSE21034. We found that patients in the high-risk group were more prone to BCR and closely associated with high-grade and advanced-stage disease progression. Outperforming clinical characteristics and nine published articles, our signature demonstrated excellent predictive performance. The patients in the low-risk group were strongly related to the high infiltration of various immune cells including CD8+ T cells and plasma B cells. Furthermore, the high-risk group with higher TMB levels and expression of immune checkpoints was more likely to benefit from immune checkpoint therapy such as PD-1 and CTLA-4 inhibitors. The sensitivity to chemotherapy, endocrine, and targeted therapy showed significant differences in the two risk groups. Our signature was a novel therapeutic strategy to distinguish the prognosis and guide treatment strategies.