Abstract
PURPOSE: To explore the clinical significance of pyruvate dehydrogenase kinase 4 (PDK4) in pan-cancer and its potential as a tumor biomarker and immunotherapy target. METHODS: Public databases (HPA, TCGA, GTEx, etc.) were used to analyze PDK4 expression, diagnostic efficacy, prognostic value, immune characteristics, genetic alterations, and immunotherapy responsiveness in pan-cancer. Targeted drugs were predicted via molecular docking. RESULTS: PDK4 is predominantly expressed in skeletal muscle and specific cell types (basal prostatic cells, skeletal myocytes, etc.) in normal tissues. In most tumors, PDK4 expression is downregulated, with high diagnostic efficacy (AUC > 0.7 for most cancers) and independent prognostic value for overall survival (OS) in multiple tumors. PDK4 is enriched in immune cells (monocytes, myeloid DC) and positively correlated with immune infiltration and checkpoint genes. High PDK4 expression improves progression-free survival (PFS) in anti-PD-L1-treated patients, and tretinoin binds stably to PDK4. CONCLUSIONS: PDK4 is a promising pan-cancer diagnostic/prognostic biomarker and potential immunotherapy target, providing a basis for personalized cancer treatment.