title: Integration and bioinformatics analysis of DNA-methylated genes associated with drug resistance in ovarian cancer.
abstract: The main obstacle to the successful treatment of 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 performed an integrative analysis of the 26 DNA-methylated genes associated with drug resistance in ovarian cancer, and the genes were further evaluated by comprehensive bioinformatics analysis including gene/protein interaction, biological process enrichment and annotation. The results from the protein interaction analyses revealed that at least 20 of these 26 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 between the phosphatase and tensin homolog (PTEN) gene and at least half of the other genes, indicating that PTEN may possess core regulatory functions among these genes. Biological process enrichment and annotation demonstrated that most of these methylated genes were significantly associated with apoptosis, which is possibly an essential way for these genes to be involved in the regulation of multidrug resistance in ovarian cancer. In addition, a comprehensive analysis of clinical factors revealed that the methylation level 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 study preliminarily explains the potential correlation 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, the treatment of ovarian cancer, and improvement of the prognosis of ovarian cancer.
authors.affiliation: Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Yan
authors.affiliation: Medical Scientific Research Centre, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China; Key Laboratory of High-Incidence Tumor Prevention and Treatment, Guangxi Medical University, Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Yin
authors.affiliation: Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Q I
authors.initials: QI
authors.lastname: Wang
authors.affiliation: Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China; Key Laboratory of High-Incidence Tumor Prevention and Treatment, Guangxi Medical University, Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors.forename: L I
authors.initials: LI
authors.lastname: Li
keywords: DNA methylation; bioinformatics; drug resistance; ovarian cancer