Serous ovarian carcinoma patients with high alpha-folate receptor had reducing survival and cytotoxic chemo-response

The alpha-folate receptor (alpha-FR) is highly-expressed in various non-mucinous tumors of epithelial origin, including ovarian carcinoma. The aim of this study was to investigate the relationship between alpha-folate receptor (alpha-FR) and the clinico-pathologic features and outcomes of serous ovarian carcinoma patients and the possible mechanism of alpha-FR to chemo-resistance. Therefore, semi-quantitative reverse-transcription polymerase chain reactions for alpha-FR expression were performed in the 91 specimens of serous ovarian carcinomas. The expression of alpha-FR in each ovarian cancer tissue specimen was defined as the ratio of density of alpha-FR to density of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In vitro apoptotic experiments were tested in the original OVCAR-3 tumor cells and various OVCAR-3 alpha-FR-transfectants. Patients with an increased alpha-FR expression level had poorer responses to chemotherapy (per alpha-FR expression level increase: odds ratio (OR): 8.97(95% confidence interval (CI): 1.40-57.36), p = 0.021). An increased alpha-FR expression level was an independently poor prognostic factor for disease free interval (DFI) (per alpha-FR expression level increase: hazard ratio (HR): 2.45 (95% CI: 1.16-5.18), p = 0.02) and had a negative impact on overall survival (OS) of these serous ovarian cancer patients (per alpha-FR expression level increase: HR 3.6 (95% CI: 0.93-13.29), p = 0.03) by multivariate analyses. alpha-FR inhibited cytotoxic drug-induced apoptosis in our in vitro apoptotic assays. alpha-FR could induce chemo-resistance via regulating the expression of apoptosis-related molecules, Bcl-2 and Bax. Therefore, alpha-FR can be a potential biomarker for the prediction of chemotherapeutic responses and clinical prognosis. It also could be the target of ovarian cancer treatment. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.