Serum pyruvate dehydrogenase kinase as a prognostic marker for cholangiocarcinoma.

Pyruvate dehydrogenase kinase (PDK) is a Ser/Thr kinase that inactivates mitochondrial pyruvate dehydrogenase and serves a key role in aerobic glycolysis, which is a hallmark of cancer cells. The present study determined the PDK expression in cholangiocarcinoma (CCA) tissues and sera to evaluate their applicability as a biomarker for CCA. Using proteomic analysis, PDK was revealed to be the most overexpressed mitochondrial protein in CCA tissues. Then, the expression of PDK isoforms in CCA tissues was examined in 15 CCA cases by immunohistochemistry. The PDK3 isoform levels in the sera were measured using a dot blot assay for 39 patients with CCA, 20 patients with benign biliary disease and 19 healthy volunteers. The results revealed a 27-fold overexpression of PDK3 in cancerous tissues when compared with adjacent non-cancerous tissues. The immunohistochemical results demonstrated that the PDK1, 2 and 3, but not the PDK4, isoforms were overexpressed in cancerous tissues. When the PDK3 levels in the sera were examined, they were significantly higher in CCA when compared with the BBD and healthy groups. The specificity and sensitivity of PDK3 as a marker for CCA were 97.5 and 33.0%, respectively, and high PDK3 levels in the sera were correlated with a short survival time for CCA. In conclusion, PDK3 can be used as a diagnostic/prognostic marker for CCA.