title: Serous ovarian carcinoma patients with high alpha-folate receptor had reducing survival and cytotoxic chemo-response.
abstract: The alpha-folate receptor (α-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 (α-FR) and the clinico-pathologic features and outcomes of serous ovarian carcinoma patients and the possible mechanism of α-FR to chemo-resistance. Therefore, semi-quantitative reverse-transcription polymerase chain reactions for α-FR expression were performed in the 91 specimens of serous ovarian carcinomas. The expression of α-FR in each ovarian cancer tissue specimen was defined as the ratio of density of α-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 α-FR-transfectants. Patients with an increased α-FR expression level had poorer responses to chemotherapy (per α-FR expression level increase: odds ratio (OR): 8.97 (95% confidence interval (CI): 1.40-57.36), p = 0.021). An increased α-FR expression level was an independently poor prognostic factor for disease free interval (DFI) (per α-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 α-FR expression level increase: HR: 3.6 (95% CI: 0.93-13.29), p = 0.03) by multivariate analyses. α-FR inhibited cytotoxic drug-induced apoptosis in our in vitro apoptotic assays. α-FR could induce chemo-resistance via regulating the expression of apoptosis-related molecules, Bcl-2 and Bax. Therefore, α-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.
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, 7, Chung-Shan South Road, Taipei, Taiwan, ROC.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Chen
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Chang
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Huang
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Chiang
authors.forename: Han-Wei
authors.initials: HW
authors.lastname: Lin
authors.forename: Chi-An
authors.initials: CA
authors.lastname: Chen
authors.forename: Chang-Yao
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D058975:Folate Receptor 1 / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D010051:Ovarian Neoplasms / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D058975:Folate Receptor 1