Elevated Circulating Lactate Levels and Widespread Expression of Its Cognate Receptor, Hydroxycarboxylic Acid Receptor 1 (HCAR1), in Ovarian Cancer

Abstract

Augmented glycolysis in cancer cells is a process required for growth and development. The Warburg effect provides evidence of increased glycolysis and lactic acid fermentation in cancer cells. The lactate end-product of glycolysis is receiving growing traction for its role as a cell signalling molecule. Ovarian cancer (OvCa) is also characterised by altered glucose metabolism. We aim to explore circulating lactate levels in patients with high-grade serous OvCa (HGSOC) and to elucidate the expression of the lactate receptor hydroxycarboxylic acid receptor 1 (HCAR1) in OvCa. HCAR1 expression was detected in patient biopsy cores using immunohistochemistry, while lactate was measured from whole blood with a Biosen-C line clinic measuring system. We noted significantly elevated lactate levels in OvCa patients (4.3 ± 1.9 mmol/L) compared with healthy controls (1.4 ± 0.6 mmol/L; < 0.0001), with an AUC of 0.96. The HCAR1 gene is overexpressed in OvCa compared to healthy controls ( < 0.001). Using an OvCa tissue microarray (>75% expression in 100 patients), high protein expression was also recorded across all epithelial OvCa subtypes and ovarian normal adjacent tissue (NAT). Lactate monitoring is a simple, cost-efficient test that can offer point-of-care results. Our data suggest that the potential of circulating lactate as a screening biomarker in OvCa merits further research attention.