Big data-based identification of methylated genes associated with drug resistance and prognosis in ovarian cancer

Abstract

It is imperative to further the understanding of the drug resistance mechanisms of ovarian cancer (OC) and to identify useful biological markers for prognosis prediction. Cormine, cBioportal, and The Cancer Genome Atlas databases were used to search microarray data of gene methylation related to OC, drug resistance in OC, and prognosis, and to analyze methylated genes potentially inducing the drug resistance in OC. Fifty-five DNA-methylated genes significantly associated with drug resistance in OC were screened, and the regulatory mechanisms underlying changes in methylation levels of these genes were systematically integrated. Enrichment and annotation of biological processes indicated that most of the above DNA-methylated genes were significantly associated with cell proliferation and cell cycle. In addition, pathway enrichment demonstrated that the above DNA-methylated genes were significantly associated with PI3K-AKT and P53 signaling pathways. Among the 55 genes, 4 were significantly associated with OC prognostic disease-free survival, namely bromodomain containing 4, PDZ domain containing 1 ( PDZK1) , phosphatase and tensin homolog, and TNF receptor superfamily member 10c; 5 were significantly related to overall survival, namely bromodomain containing 4, PDZK1 , PIK3C2B , Rh associated glycoprotein, and DYRK ; among them, the degree of methylation of TNF receptor superfamily member 10c, PDZK1 , and Rh associated glycoprotein genes was significantly correlated with mRNA expression. Furthermore, PDZK1 , Rh associated glycoprotein, and TNF receptor superfamily member 10c genes showed significant hypomethylation in drug-resistance tissues of OC, and their mRNAs had significantly high expression. The association between the methylation of these 55 genes and OC and drug resistance in OC, in addition to bioinformatics analyses clarify the important mechanisms of gene methylation in the development, progression, and drug resistance of OC.

Relationship between insulin resistance and endometrial cancer was revealed by gene screening

“…PIK3C2B can control cell invasion partly by regulating the MEK/ERK pathway and partly by activating additional signalling pathways that modulate prostate cancer cell migration 33 . And in a previous study, PIK3C2B had impacts on prognostic OS of ovarian cancer(OC), resulting in a reduction in the median survival time of OC by 7 to 10 months 34 . Then PIK3C2B participates in PI3K-Akt signaling pathway, and PI3K network belongs to the most common events in human cancers 34 , Philip et al reported that inhibition of PI3K/Akt/mTOR signaling increased the sensitivity of endometrial carcinoma cells to some targeted therapies 35 , so blocking PIK3C2B may be an immunotherapeutic pathway for the treatment of endometrial carcinoma.…”

Relationship Between Insulin Resistance and Endometrial Cancer: Determination of Key Genes and Pathways

“…PIK3C2B is strongly related to tumour stage and vessel invasion, which was closely and positively connected with prognosis in colon cancer 31 .In addition, PIK3C2B can regulate different cell functions, such as cell proliferation, invasion and cancer progression 32 .PIK3C2B can control cell invasion partly by regulating the MEK/ERK pathway and partly by activating additional signalling pathways that modulate prostate cancer cell migration 32 .And in a previous study,PIK3C2B had impacts on prognostic OS of ovarian cancer(OC), resulting in a reduction in the median survival time of OC by 7 to 10 months 33 .Then PIK3C2B participates in PI3K-Akt signaling pathway,and PI3K network belongs to the most common events in human cancers 33 ,Philip et al reported that inhibition of PI3K/Akt/mTOR signaling increased the sensitivity of endometrial carcinoma cells to some targeted therapies 34 ,so blocking PIK3C2B may be an immunotherapeutic pathway for the treatment of endometrial carcinoma.…”

Role of Midkine in Cancer Drug Resistance: Regulators of Its Expression and Its Molecular Targeting

“…Mirkin et al have shown that cisplatin-resistant ovarian cancer cells express higher amounts of MDK than their drug-sensitive counterpart [19]. Big data-based identification and bioinformatics analysis have found the association of MDK as one of the 55 genes that are involved in the development, progression, and drug resistance of ovarian cancer [60].…”