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

Mol Oncol. 2012 Jun;6(3):360-9. doi: 10.1016/j.molonc.2011.11.010. Epub 2011 Dec 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cystadenocarcinoma, Serous / drug therapy*
  • Cystadenocarcinoma, Serous / metabolism*
  • Female
  • Flow Cytometry
  • Folate Receptor 1 / metabolism*
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • In Vitro Techniques
  • Ovarian Neoplasms / metabolism*

Substances

  • Antineoplastic Agents
  • Folate Receptor 1