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.

Publication DOI: https://doi.org/10.3390/jcm12010217
Divisions: College of Health & Life Sciences > Aston Medical School
Additional Information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)
Uncontrolled Keywords: lactate,liquid biopsy,screening,HCAR1,high-grade serous ovarian cancer (HGSOC),ovarian cancer (OvCa),biomarker
Publication ISSN: 2077-0383
Last Modified: 02 Dec 2024 08:48
Date Deposited: 23 Jan 2023 13:57
Full Text Link:
Related URLs: https://www.mdp ... 7-0383/12/1/217 (Publisher URL)
PURE Output Type: Article
Published Date: 2022-12-27
Published Online Date: 2022-12-27
Accepted Date: 2022-12-20
Submitted Date: 2022-11-03
Authors: Kerslake, Rachel
Panfilov, Suzana
Mustafa, Nashrah
Hall, Marcia
Kyrou, Ioannis (ORCID Profile 0000-0002-6997-3439)
Randeva, Harpal S
Karteris, Emmanouil
Godfrey, Richard

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