Guan Bin, Lu Qi, Chen Junyu, Fang Jingyi, Liu Zhenyu, Li Wei, Zhang Lingyun, Xu Guoxiong
Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Cell Biol Int. 2025 Jun;49(6):674-691. doi: 10.1002/cbin.70015. Epub 2025 Mar 11.
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 mA 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 mA modification inhibition. These data highlight the potential application of FLOT1 as a diagnostic marker and a therapeutic target for patients with OC.
卵巢癌（OC）是一种致命疾病，在全球范围内缺乏用于诊断的精确标志物。我们之前的研究表明，浮舰蛋白-1（FLOT1）在OC组织中过表达。为了提高诊断的敏感性和准确性，我们评估了OC患者血清中FLOT1的水平，发现与健康对照者（p < 0.01）及良性肿瘤患者（p < 0.05）相比，OC患者血清中FLOT1以及CA125的浓度显著升高。在OC患者中，FLOT1和CA125的检测率（高于临界值上限）分别为77.78%和72.22%，两者联合检测时检测率提高到88.89%。在植入人OC细胞后的裸鼠血清中证实了FLOT1升高。血清中高水平的FLOT1蛋白与OC组织中FLOT1蛋白的过表达呈正相关。此外，与正常卵巢上皮细胞相比，OC细胞中FLOT1 mRNA的mA修饰水平显著升高，导致FLOT1 mRNA表达增加。应用甲基化抑制剂3-脱氮腺苷可降低OC细胞中FLOT1 mRNA的表达，并在异种移植小鼠模型中抑制肿瘤形成。总之，本研究表明FLOT1是OC的一种新型血清生物标志物，可通过抑制mA修饰作为靶点。这些数据突出了FLOT1作为OC患者诊断标志物和治疗靶点的潜在应用价值。
