Fatty Acid-binding Protein 4 And Its Effects On Cell Proliferation And Metastasis Of Human Epithelial Ovarian Cancer

Background and aims: To investigate the relationship between fatty acid binding protein 4（FABP4）and epithelial ovarian cancer（EOC）omentum metastasis,cell proliferation and migration of ovarian cancer.Methods: Histological experiment : 72 cases primary lesion and omentum tissues,serum samples of who underwent cytoreductive surgery in patients with ovarian cancer,35 cases ovarian epithelial tissues and serum specimens of who underwent appendectomy of uterus in patients with uterine fibroids,21 cases omentum tissues of who underwent metabolic weight loss surgery in female patients with obesity from January 2019 to August 2021 in the first affiliated hospital of Anhui medical university were included this study.The expression of FABP4 in each group was detected by QRT-PCR and immunohistochemistry.Serum FABP4 concentration in each group was detected by ELISA.The relationship between FABP4 expression and clinical and pathological factors related to EOC omentum metastasis was analyzed by univariate analysis.In vitro cell experiments: treated with rh FABP4（100ng/ml）and FABP4 inhibitor BMS309403（20μmol/L）,cell proliferation and cell migration ability were investigated by CCK8 and scratch assay.The level of FABP4 of SKOV3 and A2780 cells in the m RNA and protein expressions were measured by using q RT-PCR and Western blot,respectively.Results: Histological tests: QRT-PCR results showed that the expression of FABP4 gene from high to low is: normal omentum,EOC omentum without metastasis,EOC omentum with metastasis,ovarian epithelium,and primary lesion of EOC;FABP4 expression in omentum tissue was significantly higher than that in primary lesionfor EOC patients.The expression of FABP4 in EOC omentum metastatic was 700 times higher than that in primary lesion of EOC（P < 0.001）,and that EOC omentum without metastasis was 2600 times higher than that in primary lesionof EOC（P < 0.0001）.The expression of FABP4 in omentum without metastasis was high（close to the level of FABP4 in normal omentum）,suggesting that FABP4 was related to EOC omentum metastasis;Immunohistochemical results showed that FABP4 protein expression in primary EOC was significantly higher than that in ovarian epithelium,and FABP4 expression was proportional to the clinical stage of EOC.The expression of FABP4 protein in normal omentum tissue was extremely high,and the expression of FABP4 protein in EOC metastatic omentum was significantly higher than that in primary EOC,while the expression of FABP4 protein in non-metastatic omentum was significantly higher than that in metastatic omentum.ELISA assay results showed that,FABP4 expression level was（6103 ± 220.4）pg/ m L in 45 patients with EOC omentum metastasis,and（5821.95 ± 653.9）pg/ml in 27 patients without EOC omentum metastasis.The expression level of FABP4 in 35 adult women（uterine fibroids）was（2813±206.00）pg/ml,and there was statistically significant difference between ECO patients and adult women（F=21.928,P < 0.01）.Clinicopathological analysis suggested that FABP4 expression was related to FIGO stage,pathological classification of ovarian cancer（serous cancer was higher than non-serous cancer）,CA125 value,residual tumor volume and omentum metastasis（P<0.01）.In vitro cell experiments: after treated with recombinant rh FABP4（100ng/ml）for 48 h,inhibition of FABP4 expressioncould suppress the growth and migration rates of two cells compared to blank control cells group（P < 0.01）.In contrast,the results indicated a increase the growth and migration rate of two cells treated with FABP4 inhibitor BMS309403（20μmol/L）for 48 h relative to thoseblank control cells group（P < 0.01）.Conclusions:1.The expression of FABP4 in normal omental tissues,metastatic or non-metastatic omentum tissues were significantly higher than that in ovarian epithelium and primary lesion of EOC,suggesting that FABP4 is a lipidophilic gene with high specific expression in omentum tissues.2.FABP4 expression in omentum tissue was significantly higher than in primary lesion of EOC for EOC patients,and FABP4 expression in omentum tissue without metastasis was higher than that in normal omentum tissue（close to the level of FABP4 in normal omentum）,suggesting that FABP4 is related to EOC omentum metastasis.Low expression of FABP4 may be an independent risk factor for EOC omentum metastasis.3.Overexpression/inhibition of FABP4 expression in EOC cell lines can significantly inhibit/promote cell proliferation and migration,and FABP4 may serve as a new potential target for treatment of EOC omentum metastasis.4.FABP4 expression is different in primary and metastatic carcinoma,suggesting that FABP4 may play a double-edged role in EOC.