Expression And Clinical Value Of FGF8 In Ovarian Cancer

Background and ObjectiveOvarian Cancer(OC)is a common gynecological malignancy in the clinic and one of the most common female-related malignancies with the highest mortality rate.Due to the concealment of ovarian cancer,the lack of typical early clinical symptoms and effective screening methods,60% to 70% of patients have been diagnosed with advanced disease when they have abdominal distension,abdominal pain or a pelvic mass.At present,the diagnosis of ovarian cancer mainly relies on imaging examination and detection of tumor markers,but its specificity and sensitivity are low.With the continuous improvement of the means of diagnosis and treatment,the treatment of ovarian cancer is mainly based on surgical treatment combined with chemotherapy.Patients with early stage ovarian cancer may be underwent comprehensive staged surgery.Patients with advanced ovarian cancer can underwent cytoreductive surgery under platinum-based neoadjuvant chemotherapy before surgery,or a sufficient amount of platinum-based combination chemotherapy after tumor cell depletion.Firbroblast growth factor 8 is a member of the fibroblast growth factor family(FGFs),which involves in the early differentiation of cells during embryonic period.At present,relevant studies have found that FGF8 has no expression or low expression in normal adult tissues,but FGF8 is overexpressed in hormone-dependent tumors or certain inflammation sites,such as prostate cancer,breast cancer and ovarian cancer.To investigate the effects of FGF8 on the development of ovarian cancer,the study collected ovarian samples and clinical data from 87 patients in Zhengzhou Central Hospital.The expression of FGF8 in normal ovarian tissue,benign ovarian tumor and epithelial ovarian cancer was detected by immunohistochemical staining,and we analyzed the relationship between the expression of FGF8 and the patient's age,clinical stage,tissue grade,tissue type,lymph node metastasis and ascites.In addition,we investigated the effect of FGF8 on the migration ability of ovarian cancer cells in vitro.Methods1.From January 2012 to December 2018,87 ovarian tissues were enrolled in Zhengzhou Central Hospital,including 47 cases of epithelial ovarian cancer,25 cases of benign ovarian tumor and 15 cases of normal ovarian tissue.The age of ovarian cancer patients ranged from 24 to 82 with an average age of 53.67.According to the International Federation of Gynecology and Obstetrics(FIGO)standard,surgical pathological stage: there were 19 cases from stage I to II,and 28 cases from stage III to IV;Histological type: 32 cases of serous carcinoma,7 cases of mucinous carcinoma,6 cases of endometrioid carcinoma and 2 cases of clear cell carcinoma;Histological grading: 9 cases of moderate-to-high differentiation,38 cases of poor differentiation;Ascites:15 cases without ascites and 32 patients with ascites;15 patients with lymph node metastasis and 32 patients without lymph node metastasis.Immunohistochemical staining was used to detect the expression of FGF8 in different ovarian tissues,and the relationship between the expression of FGF8 and characteristics of clinical cases was analyzed.2.We constructed the FGF8 overexpressing lentiviral vector and packaged the lentiviral particle HBLV-h-FGF8-3xflag-GFP-PURO,then made it infect SKOV-3 and OVCAR-8 cells to overexpress FGF8.The blank group and the negative control group infected with HBLV-GFP-PURO were set.We detected the expression of FGF8 protein in ovarian cancer cells by Western blot,and explored the effect of FGF8 on the migration of ovarian cancer cells by Wound heaing assay.3.Statistical analysis was analyzed by SPSS 20.0 software.The comparison between the groups was analyzed by chi-square test and ANOVA.The multiple comparisons between groups were performed by LSD test.The difference was statistically significant at P<0.05.Results1.Compared with benign ovarian tumor and normal ovarian tissues,the expression of FGF8 was significantly higher in ovarian cancer tissues(P<0.05).but there was no significant difference between benign ovarian tumor and normal ovarian tissue(P>0.05).The expression level of FGF8 in ovarian cancer was statistically different from clinical clinicopathological stage and lymph node metastasis(P<0.05),however there was no difference with age,tissue grade,tissue type and ascites(P>0.05).2.SKOV-3 and OVCAR-8 cell lines were infected by Lentivirus,Western blot technology results showed that FGF8 protein of the experimental group infected with HBLV-h-FGF8-3xflag-GFP-PURO expressed highly;In addition,the migration ability of the experimental group was higher than blank group and negative control group,but there was no significant difference between blank group and negative control group.Conclusions1.FGF8 is highly expressed in ovarian cancer tissues and is associated with clinical stage and lymph node metastasis of ovarian cancer;2.FGF8 promotes the migration of ovarian cancer cells in vitro.