Overexpression of lactate dehydrogenase A in cholangiocarcinoma is correlated with poor prognosis

Abstract

Lactate dehydrogenase A (LDHA), a key metabolic enzyme, plays a crucial role in the final step of anaerobic glycolysis. Overexpression of LDHA is observed in many human malignancies in association with tumor progression. The purpose of this study was to investigate LDHA expression pattern during carcinogenesis, its clinico-pathological association, and evaluate the prognostic value of LDHA in CCA patients. LDHA expression was investigated using immunohistochemistry technique in both hamster- (n=60) and human-CCA tissues (n=82). Plasma LDH from healthy control (n=40) and CCA patients (n=29) were determined using an enzymatic based assay. The association of LDHA expression with clinicopathological findings and prognostic value were evaluated by statistical analysis. In the CCA hamster model, an increase of LDHA expression was associated with the progression of CCA-genesis. Higher LDHA overexpression was associated with shorter survival of CCA patients. Multivariate analysis indicated that LDHA expression including histological type were independent prognostic risk factor of patient’s survival. However, there was no difference in plasma LDH level between CCA patients and healthy controls. LDHA expression is involved in cholangio-carcinogenesis. Overexpression of LDHA can be a marker of poor prognosis in CCA patients and it might be a potential target for CCA treatment.