Background: Pyroptosis is a form of programmed cell death accompanied by specific inflammatory and immune responses, and it is closely related to the occurrence and progression of various cancers. However, the roles of pyroptosis-related genes (PRGs) in the prognosis, treatment response, and tumor microenvironment (TME) of prostate cancer (PCa) remain to be investigated.Methods: The mRNA expression data and clinical information of PCa patients were obtained from the Cancer Genome Atlas database (TCGA) and the cBioPortal for Cancer Genomics website, and the 52 PRGs were obtained from the published papers. The univariate, multivariate, and LASSO Cox regression algorithms were used to obtain prognostic hub PRGs. Meanwhile, qRT-PCR was used to validate the expression of hub genes between PCa lines and normal prostate epithelial cell lines. We then constructed and validated a risk model associated with the patient’s disease-free survival (DFS). Finally, the relationships between risk score and clinicopathological characteristics, tumor immune microenvironment, and drug treatment response of PCa were systematically analyzed.Results: A prognostic risk model was constructed with 6 hub PRGs (CHMP4C, GSDMB, NOD2, PLCG1, CYCS, GPX4), and patients were divided into high and low-risk groups by median risk score. The risk score was confirmed to be an independent prognostic factor for PCa in both the training and external validation sets. Patients in the high-risk group had a worse prognosis than those in the low-risk group, and they had more increased somatic mutations, higher immune cell infiltration and higher expression of immune checkpoint-related genes. Moreover, they were more sensitive to cell cycle-related chemotherapeutic drugs and might be more responsive to immunotherapy.Conclusion: In our study, pyroptosis played a significant role in the management of the prognosis and tumor microenvironment of PCa. Meanwhile, the established model might help to develop more effective individual treatment strategies.

To analysis the expression of Leucine‑rich repeat fibronectin type 3 domain containing family genes(LRFNs) in prostate cancer (PCa) and its relationship with clinical features and prognosis. The PCa gene expression profiles were collected from UCSC Xena, and corresponding clinical information was extracted from the cBioPortal website. R and Cytoscape software and online tools such as HPA, cBioPortal, LinkedOmics, String, Metascape, and TIMER2 were used for bioinformatics analysis. LRFN1/2 were upregulated in various tumor tissues, including PCa, while the expression of LRFN3/4/5 were downregulated. LRFN1/2/4 were associated with disease-free survival (DFS) in PCa. LRFN4 was also associated with Gleason score and TNM staging. The protein-protein interaction (PPI) network analysis indicates that the LRFN protein family binds to the Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation protein or 14-3-3 protein(YWHA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the LRFNs and its 250 co-expressed genes are involved in protein binding and transmembrane transport, cell cycle regulation, and the PI3K-Akt pathway, etc. Besides, upregulation of the LRFN5 was correlated with the increased infiltration of immune cells such as B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, dendritic cells, and the increased expression levels of various immune molecules. LRFNs have an essential role in the development and progression of PCa. LRFN1/2 expression is upregulated in PCa and LRFN3/4/5 expression is downregulated; LRFN1/2/4 may serve as potential prognostic biomarkers in PCa. LRFN3 and LRFN5 may be involved in regulating alterations of the immune microenvironment in PCa tumors.