Expression and prognostic significance of pyruvate dehydrogenase kinase 1 in bladder urothelial carcinoma.

Muscular infiltrating bladder urothelial carcinoma (MIBC) is a highly malignant disease with a poor prognosis. Radical cystectomy is the standard treatment. However, due to surgery and postoperative complications, the quality of life of patients is seriously affected. Therefore, it is increasingly important to find prognostic markers and new therapeutic targets for MIBC. Here, we investigated the expression of PDK1, a key regulator of glucose metabolism, in bladder urothelial carcinoma (BLCA) and its effect on prognosis. The expression pattern of PDK1 was examined by bioinformatics analysis and immunohistochemistry. A total of 101 cases of BLCA were selected for tissue microarrays (TMAs) that contained both tumour and paired normal tissues. We demonstrated that PDK1 expression was correlated with tumour grade and Ki67expression in our TMA cohort (all p values < 0.05). Kaplan-Meier survival analysis showed that patients with MIBC with high PDK1 expression had a worse prognosis than patients with low PDK1 expression (p = 0.016). Multifactor risk analysis showed that increased PDK1 expression was an independent prognostic factor affecting the overall survival of MIBC patients. GSEA showed that the mTOR pathway, HIF pathway, glycolysis, PI3K/AKT/mTOR signalling, etc. were differentially enriched in the PDK1 high expression phenotype. Hence, PDK1 may be a prognostic and therapeutic target for MIBC.