Study On The Relationship Between Multidrug Resistance And DNA Methylation In Epithelial Ovarian Cancer

Ovarian cancer is a malignant tumour that is a serious threat to women’s health.Most of these tumours easily develop drug resistance in the course of post-surgery chemotherapy. And DNA methylation is one of the important regulatory mechanisms for the development of ovarian cancer multidrug resistance.Therefore,it’s significance for us to understanding the the regulatory mechanism between DNA methylation with drug reisitance and clinical factors. Using a PubMed database search,27 methylated genes that were reported to be associated with the regulation of ovarian cancer drug resistance were filtered out. Among the 27 methylated genes that are associated with the regulation of ovarian cancer drug resistance, at least half respond to ovarian cancer drug resistance by directly or indirectly involving an apoptosis signalling pathway. Apoptosis may be an important way for methylated genes to be involved in the regulation of ovarian cancer drug resistance.In addition, This review also conducted an integrated analysis of the relationship between the integrated 27 methylated genes and ovarian cancer malignant clinical behaviour and prognosis factors. In summary, this study explains the potential relationship between methylated genes and drug resistance in ovarian cancer with the potential to guide our understanding of the regulation of ovarian cancer drug resistance by gene methylation, treatment and improvement of the prognosis of ovarian cancer.The main obstacle to a successful treatment for ovarian cancer is the development of drug resistance to combined chemotherapy. Among all the factors associated with drug resistance, DNA methylation apparently plays a critical role. In this study, we integrative summarized the 27 DNA-methylated genes associate with drug resistance in ovarian cancer, and the genes were further analyzed by comprehensive bioinformatics analysis including gene/protein interaction, biological process enrichment and annotation. The results from protein interaction analyses showed that at least 20 of these 27 methylated genes are present in the protein interaction network, indicating that they interact with each other, have a correlation in function, and may participate as a whole in the regulation of ovarian cancer drug resistance. There is a direct interaction of the phosphatase and tensin homolog (PTEN) gene with at least half of the other genes, indicating that PTEN may have core regulatory functions among these genes. Biological process enrichment and annotation showed that most of these methylated genes were significantly associated with apoptosis, possibly an important way for these genes to be involved in the regulation of multidrug resistance in ovarian cancer. In addition, a comprehensive analysis of clinical factors found that the methylation levels of genes that are associated with the regulation of drug resistance in ovarian cancer was significantly correlated with the prognosis of ovarian cancer. Overall, this article preliminarily explains the potential relationship between the genes with DNA methylation and drug resistance in ovarian cancer. This finding has significance for our understanding of the regulation of resistant ovarian cancer by methylated genes, treatment of ovarian cancer, and improvement of the prognosis of ovarian cancer.Objective:Adenomatous polyposis coli(APC) gene is known as tumor suppressor gene. The inactivation of APC plays a key role in the development of ovarian cancer.APC hypermethylation can lead decreased or even silenced gene expression level.This regulation is the impartant epigenetic regulation of ovarian cancer multidrug resistance.There are a number of studies discussed about the relation of APC methylation and ovarian cancer.However,these studies are small simple studies,and the results are not consistent. Therefore,to futher confirm the relationship between APC and ovarian cancer,we conduct a meta analysis.Methods:Search softwares such as PUBMED, EMBASE, Web of science, and CNKI datab were used to identified eligible studies.State11.0 software was used for statistical analysis such as RR risk value, STATE 11.01 software for statistical analysis such as RR risk value, heterogeneity and publication bias.Result:Nine studies,with 641 ovarian cancer patiens and 377 controls were include in the meta analysis. Statistical results shows that:The pooled odds ratio was 6.19(95%CI:4.08-9.41,P<0.05) in the cancer group versus the control group under fix effects model.The pooled odds ratio was 5.88(95%CI:3.662-9.450.P<0.05).Conclusion:The result suggest that RASSF1A promoter methylation had a strong association with ovarian cancer.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...