Abstract
Abstract Objective To investigate folate-receptor 1 (FOLR1) expression in ovarian cancer and its association with patient prognosis. Methods TCGA and Oncomine databases were used to collect data about FOLR1 mRNA expression in multiple carcinomas. FOLR1 mRNA expression levels in ovarian cancer samples and corresponding adjacent normal ovary tissue were compared. A protein-protein interaction (PPI) network was constructed using the STRING database of FOLR1 and relevant genes. The overall survival (OS) and progression free survival (PFS) rates of ovarian cancer patients in high- and low- FOLR1 expression groups were compared by log-rank test. Sixty-six ovarian epithelial carcinoma samples were included in the study, and tumor specimens of the 66 cases were tested for FOLR1 protein expression by an immunohistochemistry assay. Results FOLR1 mRNA was significantly elevated in ovarian cancer compared to other carcinomas. FOLR1 mRNA expression levels were significantly higher in tumor tissues than in the corresponding normal tissues (P<0.05) of ovarian cancer patients. The PPI network indicated that the local clustering coefficient was 0.898, indicating that the PPI network was enriched significantly (P<0.05). The median PFS values were 22.39 and 19.00 months for lowand high-FOLR1 expression groups, respectively, with significant statistical difference between the two (HR=1.26, 95%CI:1.09-1.45, P<0.05). FOLR1 protein expression was correlated with tumor differentiation (P<0.05) in ovarian cancer patients. However, its levels were not correlated with patient age, tumor diameter, lymph node metastasis or FIGO stage (P>0.05). Conclusion FOLR1 is upregulated in epithelial ovarian cancer, and its expression is correlated with patients’ progression free survival, making it a valuable biomarker for prognosis.
Highlights
folate-receptor 1 (FOLR1) mRNA expression was significantly elevated in ovarian cancer compared to other carcinomas (Figure 1A)
It remains unclear whether FOLR1 is upregulated in the tumor tissue of ovarian cancer patients, as well as whether its expression level is correlated with the patient’s prognosis
We carried out this bioinformatics study to evaluate FOLR1 expression, functional enrichment, related signaling pathways and relationship with patients’ prognoses in ovarian cancer, further validated these results through an immunohistochemistry assay
Summary
Ovarian cancer is one of the most frequently diagnosed gynecological malignancies, with epithelial ovarian cancer accounting for 80% to 96% of all diagnosed ovarian carcinomas [1]. Most patients have developed to a late stage of disease progression by the time of diagnosis; the prognosis is poor, with the 5-year survival rate of 20% - 30% [2, 3]. Early detection, intervention and accurate evaluation of prognosis are important for ovarian cancer patients. TP53, Rb1, BRCA1 and BRCA2 have been confirmed as cancer-related genes and tumor suppressor genes involved in ovarian cancer, but the survival implications of these genes in ovarian cancer patients are still controversial. About 96% of epithelial serous ovarian cancers are found to involve TP53 gene mutations [5, 6]. Havrilesky et al confirmed that TP53 overexpression is not an independent prognostic factor of overall survival (OS) or progression free survival (PFS) in epithelial ovarian cancer patients [7]
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