Identification and Experimental Verification Reveal SLC2A3 Associated With Prognosis and Immune Infiltration in Colon...

Colon adenocarcinoma (COAD) exhibits marked molecular heterogeneity that limits accurate prognostic prediction and therapeutic stratification. Parthanatos, a poly (ADP-ribose) polymerase-1 (PARP1)-dependent form of regulated cell death, has been implicated in tumor biology, yet its relevance in COAD remains poorly understood. In this study, we systematically characterized parthanatos-associated genes (PAGs) using integrated transcriptomic analyses from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Distinct parthanatos-related molecular subtypes with significantly different clinical outcomes and immune landscapes were identified. A parthanatos-based prognostic scoring system was constructed using machine learning algorithms and validated in an independent cohort, demonstrating robust predictive performance and independent prognostic value. High PAG scores were associated with advanced disease stage, altered immune infiltration, increased tumor mutation burden (TMB), and differential sensitivity to chemotherapy and predicted immunotherapy response. Single-cell RNA sequencing further revealed broad cellular expression of PAG, while preliminary in vitro experiments suggested that solute carrier family 2 member 3 (SLC2A3), the most prominent risk gene in the prognostic model, may promote COAD cell proliferation and invasion, although these findings require validation in additional models. Collectively, our findings establish parthanatos as a clinically relevant regulatory axis in COAD and provide a novel framework for prognosis assessment and therapeutic targeting.