Characterization of Immunogenic Cell Death Related Molecular Subtypes and Its Therapeutic Implications for Prostate Adenocarcinoma

Abstract

This study investigates immunogenic cell death (ICD)-related gene expression patterns in prostate adenocarcinoma (PRAD), explores the potential for ICD activation to induce anticancer effects, and identifies molecular subtypes in PRAD. Datasets from TCGA and GEO were analyzed using R software to assess ICD-related gene expression changes. Up-regulated genes included EIF2AK3, FOXP3, BAX, PDIA3, CALR, and CASP8, while down-regulated genes included IL1R, PIK3CA, IL17A, and others. Western blot confirmation supported the up-regulation of EIF2AK3, FOXP3, BAX, PDIA3, CALR, and CASP8. Clustering 497 samples based on 33 ICD-related genes revealed three molecular subtypes, with distinct gene functions and varying PD-L1 expression levels. The PRAD tumor microenvironment exhibited an abundance of resting dendritic cells and rare activated dendritic cells. This study suggests that diverse ICD-related genes are expressed in PRAD, leading to the classification of three molecular subtypes, which could guide precise molecular-level treatments. Additionally, the presence of resting dendritic cells in the PRAD tumor microenvironment hints at the potential for ICD-based therapies to activate these cells for anti-tumor effects.