Prediction of Prostate Adenocarcinoma Recurrence Prognosis and Immune Status Through 6-Acetoxy-Anopterine Resistance-Associated Programmed Cell Death Genes

Purpose: This study aims to reveal the potential mechanism and potential prognostic markers of programmed cell death (PCD) genes associated with 6-acetoxy-anopterine (6-AA) resistance in prostate adenocarcinoma (PRAD). Patients and Methods: The differentially expressed programmed cell death genes (DEPGs) associated with 6-AA resistance were revealed based on the The Cancer Genome Atlas (TCGA)-PRAD database. Then, a prognostic risk prediction model was established. Moreover, the relationship between the risk model and the immune microenvironment of PRAD samples was revealed, followed by the characteristics and mechanisms investigation of immune cell infiltration in different risk groups. Furthermore, the application prospects of the risk model in predicting drug response sensitivity were explored. Finally, the verification analysis was performed on signature genes using qPCR analysis. Results: A total of totally 57 DEPGs were screened, and these genes mainly assembled in cysteine-type endopeptidase activity functions. The nomogram and survival analysis proved the prognostic value of signatures. Immune infiltration analysis revealed the dyregulation of memory CD4+ T cells between different risk groups. Moreover, 3 clusters were revealed in current study. Finally, the mRNA expression levels of six signatures (TOP2A, PABPN1, BCL2L12, TRIM14, PIK3R1 and LAPTM4B) in the verification analysis were consistent with the findings of our current bioinformatic study. Conclusion: TOP2A, PABPN1, BCL2L12, TRIM14, PIK3R1 and LAPTM4B were novel PCD-related prognostic markers for PRAD. BCL2L12 might take part in the resistance of 6-AA in PRAD via the cysteine-type endopeptidase activity pathway. Keywords: prostate adenocarcinoma, programmed cell death, 6-acetoxy-anopterine resistance, prognostic gene, qPCR