Functional Folate Receptor Alpha Is Elevated in the Blood of Ovarian Cancer Patients

Background: Despite low incidence, ovarian cancer is the fifth leading cause of cancer deaths and it has the highest mortality rate of all gynecologic malignancies among US women. The mortality rate would be reduced with an early detection marker. The folate receptor alpha (FR alpha) is one logical choice for a biomarker because of its prevalent overexpression in ovarian cancer and its exclusive expression in only a few normal tissues. In prior work, it was observed that patients with ovarian cancer had elevated serum levels of a protein that bound to a FR alpha-specific monoclonal antibody relative to healthy individuals. However, it was not shown that the protein detected was intact functional FR alpha. In the current study, the goal was to determine whether ovarian cancer patients (n = 30) had elevated serum levels of a fully functional intact FR alpha compared to matched healthy controls (n = 30). Methodology/Principal Findings: FR alpha levels in serum were analyzed by two methods, immunoblotting analysis and a radiolabeled folic acid-based microfiltration binding assay. Using the immunoassay, we observed that levels of FR alpha were higher in serum of ovarian cancer patients as compared to controls. Similar results were also observed using the microfiltration binding assay, which showed that the circulating FR alpha is functional. Importantly, we also found that the levels of FR alpha were comparable between early and advanced stage patients. Conclusions: Our results demonstrate that ovarian cancer patients have elevated levels of functional intact FR alpha. These findings support the potential use of circulating FR alpha as a biomarker of early ovarian cancer.