Expression And Significance Of VEGF, MiR-205and Target Protein Ezrin, Lamin A/C In Ovarian Cancer

BackgroundEarly metastasis is a malignant feature of ovarian cancer; however, its metastatic mechanism remains unclear. Vascular endothelial growth factor (VEGF), which could promote tumor cell growth, invasion and metastasis, highly expressed in serum and specimen of ovarian cancer. In previous study of comparative proteomics Ezrin and LaminA/C were found, which were closely associated with invasion and metastasis of epithelial ovarian cancer in VEGF-induced epithelial ovarian cancer cell line HO-8910. We speculated that VEGF may have a direct or indirect regulation for Ezrin and LaminA/C, which involve in invasion and metastasis of ovarian cancer. In our previous work,3’UTR of Ezrin and LaminA/C was predicted to have binding sites for miRNA using the bioinformatics methods. These results suggest that there may be a close correlation between miR-205and these two proteins under VEGF treatment. Additionally, miRNA expression profiling was detected by miRNA gene chip in VEGF-induced HO-8910, and the results showed that miR-205was up-regulated. VEGF may partially regulate Ezrin and LaminA/C protein to involve in invasion and metastasis of epithelial ovarian cancer via miR-205.ObjectiveTo further explore the expression and clinical significance of VEGF, miR-205and target protein Ezrin, Lamin A/C in ovarian cancer.MethodsELISA was used for detecting the level of VEGF in serums of epithelial ovarian cancer and healthy volunteers; Immunohistochemistry was used for detecting the expression of vascular endothelial growth factor receptor1(VEGFR-1), VEGFR-1, Ezrin, LaminA/C and the MVD (micro-vessel density) of CD31in epithelial ovarian cancer, benign ovarian and normal ovarian specimens; Immunocytochemical technique was used for detecting the expression of VEGFR-1and VEGFR-2in four human ovarian cancer cell lines; Real-time PCR was used for detecting the expression of miR-205, Ezrin and LaminA/C in epithelial ovarian cancer, benign ovarian and normal ovarian specimens.Results(1) The expression of VEGF in serums of epithelial ovarian cancer patients (101.48±19.44) was significantly higher than in that of healthy volunteers (30.69±3.13)(P<0.05).(2) The positive expression rates of VEGFR-1and VEGFR-2in epithelial ovarian cancer specimens were75.9%and91.4%respectively, which were significantly higher than that in benign ovarian and normal ovarian specimens (P<0.05); No differences were observed in the positive expression rates of VEGFR-1and VEGFR-2between benign ovarian and normal ovarian specimens (P>0.05).(3) The strong positive expression of VEGFR-1and VEGFR-2were detected in four human ovarian cancer cell lines.(4) The average level of MVD in epithelial ovarian cancer specimens (7.56±0.508), it was significantly higher than that in normal ovarian specimens was (1.22±0.556)(P<0.05); The average level of MVD in epithelial ovarian cancer specimens (7.56±0.508), which was significantly higher than that in benign ovarian specimens was (0.7±0.389)(P<0.05); No differences were observed in the average level of MVD between benign ovarian and normal ovarian specimens (P>0.05).(5) The positive expression rates of Ezrin and LaminA/C in epithelial ovarian cancer specimens were51.7%and60.3%respectively, which were significantly lower than that in benign ovarian and normal ovarian specimens (P<0.05); No differences were observed in the positive expression rates of Ezrin and LaminA/C between benign ovarian and normal ovarian specimens (P>0.05).(6) The relative expression level of miR-205in epithelial ovarian cancer specimens, which was significantly higher than that in normal ovarian specimens (P<0.05); the relative expression level of miR-205in epithelial ovarian cancer specimens, which was clearly higher than that in benign ovarian specimens, but there was no statistical significance (P>0.05); the relative expression level of Ezrin and LaminA/C mRNA in epithelial ovarian cancer specimens (0.0263±0.00335) and (0.0596±0.00686) respectively, which were significantly lower than those in normal ovarian specimens were (0.0452±0.00461) and (0.2119±0.02007)(P<0.05); the relative expression level of Ezrin and LaminA/C mRNA in epithelial ovarian cancer specimens (0.0263±0.00335) and (0.0596±0.00686) respectively, which were clearly lower than that in benign ovarian specimens were (0.0287±0.01108) and (0.0888±0.01924), but there was no statistical significance (P>0.05).Conclusion(1) VEGF is significantly expressed in serums of epithelial ovarian cancer patients.(2) miR-205is up-regulated in epithelial ovarian cancer specimens.(3) Ezrin and LaminA/C are down-regulated in the epithelial ovarian cancer samples examined.(4) VEGF, miR-205and target protein Ezrin, Lamin A/C involve in invasion and metastasis of epithelial ovarian cancer.