Serum Free Fatty Acids and G-Coupled Protein Receptors Are Associated With the Prognosis of Epithelial Ovarian Cancer

PURPOSE: Fatty acid metabolism plays key role in cancer development, and free fatty acid receptors (FFARs) are involved in many cancers. However, the correlation between serum free fatty acids (FFAs)/FFARs levels and ovarian cancer (OC) prognosis remains largely unclear. METHODS: A retrospective review of 534 primary OC patients and 1049 women with benign ovarian tumors was performed. Serum FFA levels data were extracted from the electronic medical record system. Repeated FFA results of 101 OC patients treated with standard chemotherapy were collected. The effects of FFAs on cells migration were evaluated in OC cell lines by Transwell assay. Gene Expression Profiling Interactive Analysis (GEPIA) was used to compare FFAR mRNA expression levels in cancer and noncancer tissues. Kaplan-Meier (KM) plotter was employed to analyze their prognostic values. SPSS 23.0 and Graphpad prism 7.0 software was used for analysis and graph construction. RESULTS: FFA levels in the serum of epithelial ovarian cancer (EOC) women were higher than in women with benign ovarian tumors independent of pathology, tumor stage,and grade. FFA levels decreased gradually after chemotherapy. FFAs enhanced the migration of OVCAR3 cells. FFAR1 mRNA expression was lower in OC cells than in control cells. FFAR3 was related to a better prognosis, and FFAR4 was related to poor prognosis in TP-53wild-type and mutated type OC, while FFAR1 and FFAR2 were related to a better prognosis in TP53 wild-type OC but FFAR2 was related to a poor prognosis in TP53-mutant OC. CONCLUSION: The FFA levels are increased in OC and decreased with chemotherapy. High expression of FFARs was related to the prognosis of OC. The prognostic value of different FFARs differs depending on whether it is a TP53 wild or TP53 mutant ovarian cancer.Targeting FFARs may be an attractive treatment strategy for EOC.