PEX3 connects peroxisomal metabolism with stem-like plasticity and therapeutic vulnerability across human cancers

Peroxisome biogenesis factor 3 (PEX3) is essential for peroxisome formation, yet its pan-cancer relevance to stemness and therapeutic response remains unclear. We integrated transcriptomic, proteomic, genomic, survival, pathway, single-cell, spatial transcriptomic, immune, immunotherapy, and pharmacogenomic datasets to characterize PEX3 across human cancers. PEX3 showed marked cancer-specific dysregulation and heterogeneous prognostic associations. Enrichment analyses associated PEX3 with cell-cycle activity, metabolic adaptation, epithelial–mesenchymal transition, pluripotency pathways, and anticancer drug resistance. Single-cell and spatial analyses localized PEX3 preferentially to malignant compartments in representative tumors. Across immunotherapy cohorts, PEX3 displayed context-dependent associations with immune features, treatment response, and survival. Pharmacogenomic analyses further identified distinct drug-sensitivity patterns and candidate compounds predicted to reverse PEX3-associated transcriptional states. PEX3 is associated with context-dependent tumor states, stemness-related features, and treatment-response patterns, supporting further mechanistic investigation and cancer-specific evaluation of its biomarker potential.