FLOT1 Is a Novel Serum Biomarker of Ovarian Cancer Targeted by N6-methyladenosine Modification Inhibition.

Ovarian cancer (OC) is a deadly disease and lacks a precise marker for diagnosis worldwide. Our previous work has shown the overexpression of flotillin-1 (FLOT1) in OC tissue. To improve diagnostic sensitivity and accuracy, we evaluated the serum level of FLOT1 in OC patients and found that the serum concentration of FLOT1 as well as CA125 was significantly increased in patients with OC compared with healthy control (p < 0.01) and those with benign tumors (p < 0.05). The detection rate (above the upper limit of a cut-off value) of FLOT1 and CA125 was 77.78% and 72.22%, respectively, in patients with OC, which was increased to 88.89% in combination. The elevation of FLOT1 was confirmed in the serum of nude mice after the implantation of human OC cells. A high level of FLOT1 protein in the serum was positively correlated with the overexpression of FLOT1 protein in OC tissues. Furthermore, the level of m(6)A modification of FLOT1 mRNA was significantly high in OC cells compared with normal ovarian epithelial cells, leading to an increase in FLOT1 mRNA expression. Application of a methylation inhibitor, 3-deazaadenosine, decreased FLOT1 mRNA expression in OC cells and suppressed tumor formation in a xenograft mouse model. In conclusion, the current study demonstrated that FLOT1 is a novel serum biomarker of OC and can be targeted by m(6)A modification inhibition. These data highlight the potential application of FLOT1 as a diagnostic marker and a therapeutic target for patients with OC.