APPLICATION OF WHOLE GENE-WIDE DNA METHYLATION ARRAY TO SCREEN AND VERIFY DIFFERENCE METHYLATION SITES OF MULTIDRUG RESISTANCE IN EPITHELIAL OVARIAN CANCER

• 1、Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, and Key Laboratory of High-Incidence-Tumor Prevention and Treatment, Ministry of Education, Nanning 530021
• 2、Life Sciences Institute,Guangxi Medical University and Key Laboratory of High-Incidence-Tumor Prevention and Treatment, Ministry of Education, Nanning 530021

Abstract：Objective:This study aims to detect different menthylation sites using genomic DNA from multiple groups of ovarian tissues by DNA methylation arrays and explore significant multidrug resistance related biological pathways and different methylation sites in epithelial ovarian cancer by gene-set enrichment pathway analysis.Method: Using 450K Infinium Methylation BeadChip to detect the different methylation sites between the 108 cases of epithelial ovarian cancer group with 54 cases of drug-resistant tissue and 54 sensitive one,54 cases of benign ovarian tumors and 54 cases of normal ovarian tissue.R software was be used to find greater different than 1-fold up-regulation or down-regulationin DNA methylation sites.We analysised the target gene of up-regulation or down-regulation DNA by GO enrichment analysis and Pathway bioinformatics analysis to predict the biological functions and involved in which signaling pathways of the differential methylation genes. And then we validate the microarray results using QRT-PCR analysis and to detect the expression of purpose DNA.And analyze the relationships between DNA methylation and clinicopathological factors. Result:A totel of 2654 different methylation DNA(incluing 7263 sites ) were detected using DNA methylation array.There were 2162 hypermethylation genes(including 6051 sites) and 452 hypomethylation genes(including 1212 sites) in ovarian cancer resistance tissue. Biological process analysis shows that the riched biology processes including Pathways in cancer, Pathways in cancer, Focal adhesion, Calcium signaling pathway, Estrogen signaling pathway, ECM-receptor interaction, PI3K-Akt signaling pathway, ErbB signaling pathway, Hippo signaling pathway, Drug metabolism - other enzymes, Phosphatidylinositol signaling system.We selected PIK3R3 and LAMA3 which are the significant different methylation genes between sensitive and resistant groups to verify the result of methylation array according QRT-PCR.Conclusion: Microarray-based screening DNA methylation sites associated with epithelial ovarian cancer multidrug resistance,which enriching the current data known target genes associated with drug resistance.We need more clinical sample to verify over array result and to further explore the molecularmechanism and the relationship between DNA methylation and multidrug resistance in epithelial ovarian cancer.?????

Keywords： oncology methylation ovarian cancer array drug resistance array verification