Folate receptor genes were up-regulated in epithelial ovarian cancer and partly associated with patients’ prognosis

Abstract

Abstract Objective The present work aimed to investigate folate receptor (FOLR1, FOLR2, FOLR3) expression, functional enrichment, signaling pathway and prognosis in ovarian cancer patients by integrated bioinformatics analysis. Methods Folate receptor (FOLR1, FOLR2, and FOLR3) mRNA expression level between epithelial ovarian cancer and corresponding normal ovarian tissue of cancer patients was compared through the TCGA database by GEPIA online analysis tool. The protein–protein interaction (PPI) network of FOLR1, FOLR2, FOLR3, and related genes were constructed through the STRING database. GO and KEGG enrichment of FOLR1, FOLR2, FOLR3, and relevant genes were analyzed. Overall survival (OS) and progression-free survival (PFS) between FOLR1, FOLR2, and FOLR3 mRNA high and low expression epithelial ovarian cancer patients were compared by log-rank test. Results FOLR and FOLR3 mRNA expression in epithelial ovarian cancer tissue were significantly higher than that of corresponding normal ovarian tissue of cancer patients (P < 0.05) The PPI network showed 53 nodes and 298 edges with the average node degree of 11.2. The local clustering coefficient was 0.744, which indicated that the protein–protein enrichment was statistically significant (P < 1.0 × 10−16). Folate receptor (FOLR1, FOLR2, and FOLR3) and relevant genes were mainly enriched in folic acid transport, methotrexate transmembrane transporter activity, antifolate resistance for biological process, molecular function, and KEGG pathway, respectively. The PFS of FOLR1 and FOLR3 high expression epithelial ovarian cancer patients was significantly lower compared to low-expression subjects with statistical significance [hazard ratio (HRFOLR1) = 1.26, 95% confidence interval (CI): 1.09–1.45, P < 0.05, HRFOLR3 = 1.22, 95% CI: 1.06–1.40, P < 0.05]. However, the OS was not statistically different between FOLR1, FOLR2, and FOLR3 low and high expression groups. Conclusion Folate receptor (FOLR1, FOLR2, and FOLR3) genes were up-regulated in epithelial ovarian cancer and partly associated with patient’s poor prognosis.