A systems biology approach to programmed cell death in prostate cancer: Biomarker discovery and therapeutic potential...

Prostatic adenocarcinoma (PRAD) is among the most common malignancies in men and is characterized by considerable genetic and epigenetic heterogeneity. Despite advances in diagnosis and treatment, options for advanced and refractory prostate cancer remain limited, which adversely affects patient prognosis. This project aims to identify diagnostic and prognostic biomarkers associated with programmed cell death (PCD) mechanisms in prostate cancer and to reposition existing drugs that target these biomarkers. Using RNA-seq and clinical data from The Cancer Genome Atlas (TCGA), differential gene expression, ROC curve, and survival analyses identified six candidate biomarkers with strong diagnostic and prognostic significance. Three small molecules - DL-PDMP, clobetasol propionate, and metoclopramide hydrochloride - capable of reversing gene expression profiles were selected for in vitro assays in a drug repositioning analysis conducted using the L1000CDS2 platform. Among these, DL-PDMP was prioritized because of its low IC₅₀ value and low toxicity to normal prostate epithelial cells. Furthermore, DL-PDMP has been shown to induce apoptosis and suppress colony formation. These findings suggest that targeting PCD-associated biomarkers is a promising strategy for prostate cancer treatment, making DL-PDMP a strong candidate for further preclinical studies.