Kerslake Rachel, Panfilov Suzana, Mustafa Nashrah, Hall Marcia, Kyrou Ioannis, Randeva Harpal S, Karteris Emmanouil, Godfrey Richard
Division of Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK.
Mount Vernon Cancer Centre, Rickmansworth Road, Northwood HA6 2RN, UK.
J Clin Med. 2022 Dec 27;12(1):217. doi: 10.3390/jcm12010217.
Background: 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. Methods: 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. Results: 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; p < 0.0001), with an AUC of 0.96. The HCAR1 gene is overexpressed in OvCa compared to healthy controls (p < 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). Conclusions: 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.
癌细胞中增强的糖酵解是生长和发育所需的过程。瓦伯格效应为癌细胞中糖酵解增加和乳酸发酵提供了证据。糖酵解的终产物乳酸作为一种细胞信号分子，其作用越来越受到关注。卵巢癌（OvCa）也具有葡萄糖代谢改变的特征。我们旨在探索高级别浆液性卵巢癌（HGSOC）患者的循环乳酸水平，并阐明乳酸受体羟基羧酸受体1（HCAR1）在卵巢癌中的表达。方法：使用免疫组织化学检测患者活检组织芯中的HCAR1表达，同时用Biosen-C line临床测量系统从全血中测量乳酸。结果：我们注意到与健康对照（1.4±0.6 mmol/L；p<0.0001）相比，卵巢癌患者的乳酸水平显著升高（4.3±1.9 mmol/L），曲线下面积为0.96。与健康对照相比，HCAR1基因在卵巢癌中过表达（p<0.001）。使用卵巢癌组织微阵列（100例患者中>75%表达），在所有上皮性卵巢癌亚型和卵巢正常相邻组织（NAT）中也记录到高蛋白表达。结论：乳酸监测是一种简单、经济高效的检测方法，可提供即时检测结果。我们的数据表明，循环乳酸作为卵巢癌筛查生物标志物的潜力值得进一步研究关注。
