Folate-receptor 1 (FOLR1) protein is elevated in the serum of ovarian cancer patients

Abstract

Objectives: Ovarian cancer is the most lethal gynecological malignancy in North America. Although survival rates are high when the disease is diagnosed at an early stage, this decreases exponentially in late-stage diagnoses. As such, there is a need for novel early detection biomarkers. Through an integrated approach to ovarian cancer biomarker discovery that combines proteomics with transcriptomics and bioinformatics, our laboratory has identified folate-receptor 1 (FOLR1) and Dickkopf-related protein 3 (Dkk-3) as putative biomarkers. The objective of this study was to measure the levels of FOLR1 and Dkk-3 in the serum of patients with ovarian cancer, benign gynecological conditions and healthy women.

Design and methods: FOLR1 and Dkk-3 were analyzed in serum of 100 ovarian cancer patients, 100 patients with benign gynecological conditions, and 100 healthy women using enzyme-linked immunosorbent assays (ELISAs). All specimens were analyzed in triplicate.

Results: FOLR1 was significantly elevated in the serum of ovarian cancer patients compared to serum of both healthy controls (P<0.0001) and patients with benign gynecological conditions (P<0.0001). Furthermore, FOLR1 was strongly correlated with CA125 as both were elevated in the serous histotype and in late-stage disease. FOLR1 did not outperform CA125 in receiver operating characteristic curve analysis and there was no significant complementarity between the two markers. Dkk-3 was not significantly different between the three serum cohorts and was not correlated with CA125.

Conclusions: FOLR1 is a new biomarker for ovarian cancer which correlates closely with CA125. The role of FOLR1 in the pathogenesis of ovarian cancer warrants further investigation.

Keywords: AUC; Biomarker; CA125; CI; Diagnostic; Dickkopf-related protein 3; Dkk-3; ELISA; FDA; FOLR1; Food and Drug Administration; NID2; OR; Ovarian cancer; ROC; ROMA; Risk of Malignancy Algorithm; area under the curve; carbohydrate antigen 125; confidence interval; enzyme-linked immunosorbent assay; folate-receptor 1; nidogen-2; odds ratio; receiver operating characteristic.