The Promoter Hypermethylation Of TGFBI Connected With Angiogenesis In Epithelial Ovarian Carcinoma Tissue

Because of ovary anatomicsite deeper,which early symptom of ovarian carcinoma is not obvious and there is lack of early diagnosis means,majority of ovarian carcinoma patients had been end-stage disease before they were discovered.At present,mortality rate of malignant tumor of ovary situates is primacy in malignant tumor of gynecology.So ovarian carcinoma has becomed one of the most attended gynecological malignancy.The detection of methylation of DNA is important method of tumorigenesis mechanism.DNA methylation of human accruing CpG nucleotide is90%,close quarter of CpG of genomic calling CpG island,and most locates in noncoding region of5’and3’.A large number of researches indicate that promoter region of CpG island methylation can lead to chromatin structure, stability of DNA, conformation of DNA and change of interactions of protein.It is the most important mechanism of repressing gene expression. DNA methylation is biosome under the catalysis of methyltransferase of DNA, S-Adenosyl-L-methionine as methyl donor, and cytosine of two nucleotide of CG of DNA selectly add methyl ionogen of phenomenon of chemical modification.In tumor cells, CpG island of cancer suppressor gene is hypermethylation,and making the neighbor related gene can not express.On the contrary, CpG island of oncogene is hypomethylation,and both of them prompt the tumor growth.Therefore,the significant change of methylation state is the most important reason of normol cells malignant. In human adenocarcinoma cells and other cells types,TGFBI is regarded as gene that transforming growth factorβ induces.It regulate proliferation of tumor cell and induce angiogenesis though combinating specific receptor of superficial of endothelial cell.And in tumor cells,studies show that the silence of TGFBI gene has familiar connection with promoter region of CpG island.The absence of TGFBI can lead to cells proliferation,whereas the pression of debase or deletion of TGFBI used to important factor of oncogenesis.Vascular Endothelial Growth Factor(VEGF) and its receptor is the most important promoting the growth factor vessels.It is a key regulator of the discharge of tumor cells,and it takes part in proliferation of tumor cell and induce angiogenesis.It is closely related growth, infiltration and metastasis.This study detect separately the promoter hypermethylation situation of TGFBI and the expression of Vegf protein in normol ovarians, benign epithelial ovarian tumor and epithelial ovarian carcinoma tissues. Then we analysised its relationship to angiogenesis.Design to provide idea and direction for early diagnosis and clinical services of epithelial ovarian carcinoma.ObjectiveTo investigate the promoter methylation of TGFBI connected with angiogenesis in epithelial ovarian carcinoma.Materials and Methods1MaterialsParaffia specimens of ovary tissues total70was obtained from the Third Affiliated Houspital of Zhengzhou University patients from August2008to March2011.No patient had received preoperative chemotherapy and radiation therapy,what refered to case history and were confirmed by pathology.Patient age was between18and70, including20normol ovarians(appendage excision by reason of uterus lesion),20benign epithelial ovarian tumor tissues and30epithelial ovarian carcinoma tissues.2Methods Methylation-specific PCR(MSP) and immunohistochemical SP methods were used to detect separately the promoter hypermethylation situation of TGFBI and the expression of Vegf protein in20normol ovarians,20benign epithelial ovarian tumor and30epithelial ovarian carcinoma paraffia tissues,and we analysised relations of each other. Then we explored its relationship to angiogenesis.3Statistical treatmentData were recorded and analyzed by using the Statistical Package for Social Sciences software version17.0,x2test were used for enumeration data. Relationship test was used for Spearman correlation analysis.Statistical significance was set at a=0.05.Results1. The methylation rate of TGFBI were10.5%(2/19),70%(21/30) in benign ovarians tissue and epithelial ovarian cancer tissue and there were obvious difference (x~2=14.219, P<0.05)2. The positive expression rate of VEGF were10%(2/20),45%(9/20),83.3%(25/30) in normol ovarian tissue,benign ovarian tissue and epithelial ovarian cancer tissue and there were obvious difference (x~2=26.298, P<0.05)3. In epithelial ovarian cancer, promoter hypermethylation of TGFBI and the expression levels of VEGF were associated,and they are take on positive correlation.(r_s=0.516, P<0.05)Conclusions1. TGFBI occurs the methylation frequently in epithelial ovarian carcinoma tissues,which might participate the oncogenesis of epithelial ovarian carcinoma.2. The promoter of TGFBI occuring the methylation is the majoy reason of VEGF expression,and the mechanism may have important action of angiogenesis in epithelial ovarian carcinoma tissues.