Aberrant Expression of Folate Metabolism Enzymes and Its Diagnosis and Survival Prediction in Ovarian Carcinoma

Abstract

This study was to validate changes in the levels of folate receptor-α (FOLR1), dihydrofolate reductase (DHFR), and methionine synthase reductase (MTRR) in the tissue of OC patients. The expression of FOLR1, DHFR, and MTRR was evaluated in 80 cases of primary OC, 50 cases of benign ovarian tumors, and 30 normal ovarian tissues. Associations between protein expression and clinicopathological characters were assessed, and diagnostic and prognostic evaluation of FOLR1, DHFR, and MTRR was performed. Results showed that upregulated FOLR1 and MTRR and downregulated DHFR were detected in OC. Patients with abnormality of FOLR1, DHFR, and MTRR tend to have a higher percentage of platinum resistance. Moreover, the areas under receiver operating characteristic curves (AUCs-ROC) for FOLR1, DHFR, and MTRR were 0.723, 0.717, and 0.714, respectively. The combination of FOLR1, DHFR, and MTRR could produce an area of 0.864 under the receiver-operating characteristic curve in distinguishing platinum-resistant patients from platinum-sensitive patients (P<0.0001). Correlations were present between the expression of FOLR1, DHFR, and MTRR. Furthermore, Kaplan-Meier curves indicated that the patients with overexpressed MTRR had a poorer overall survival time compared to those with low expression (P<0.05). Thus, folate metabolic enzymes could provide a potential promising biomarker for diagnosis platinum-resistant in OC.