Genome-wide DNA methylation profiling in ectopic and eutopic of endometrial tissues.

PURPOSE: Endometriosis is a gynecological disease that causes the uterine lining to appear in other organs outside the uterus. As DNA methylation has an important role in this disorder, its profiling can reveal new information to improve the diagnosis and treatment of endometriosis patients. METHODS: We conducted a genome-wide methylation profiling of ectopic and eutopic endometrial tissues from women with and without endometriosis using Infinium Human Methylation 450K BeadChip arrays. DNA methylation samples were collected from nine ectopic and nine eutopic endometrial tissues of endometriosis and six endometrial tissues of healthy controls. RESULTS: Correlation heatmaps and the principal component analysis divided the samples into two clusters, one consisting of all ectopic samples and the other consisting of both eutopic and control samples unexpectedly without segregation between them. The assay identified a group of methylated genes that were overrepresented in biological processes, including abnormality in signaling, development, and adhesion of cells. Pathway analysis revealed disruption in HTLV infection pathways, PI3K-Akt, oxytocin, and relaxin signaling. Moreover, we found eutopic lesions are strongly associated with autoimmune disease. CONCLUSIONS: Our results confirmed the role of DNA methylation alternations in endometriosis development and pathogenesis. Our finding suggests aberrant DNA methylation can activate several signaling pathways including PI3k-AKT signaling, relaxin, and oxytocin which are associated with the pathogenesis of endometriosis.

Parallel molecular alteration between Alzheimer's disease and major depressive disorder in the human brain dorsolateral prefrontal cortex: an insight from gene expression and methylation profile analyses.

Alzheimer's disease (AD) and major depressive disorder (MDD) are comorbid neuropsychiatric disorders that are among the leading causes of long-term disability worldwide. Recent research has indicated the existence of parallel molecular mechanisms between AD and MDD in the dorsolateral prefrontal cortex (DLPFC). However, the premorbid history and molecular mechanisms have not yet been well characterized. In this study, differentially expressed gene (DEG), differentially co-expressed gene and protein-protein interaction (PPI) network propagation analyses were applied to gene expression data of postmortem DLPFC samples from human individuals diagnosed with and without AD or MDD (AD: cases = 310, control = 157; MDD: cases = 75, control = 161) to identify the main genes in the two disorders' specific and shared biological pathways. Subsequently, the results were evaluated using another four assessment datasets (n1 = 230, n2 = 65, n3 = 58, n4 = 48). Moreover, the postmortem DLPFC methylation status of human subjects with AD or MDD was compared using 68 and 608 samples for AD and MDD, respectively. Eight genes (XIST, RPS4Y1, DDX3Y, USP9Y, DDX3X, TMSB4Y, ZFY and E1FAY) were common DEGs in DLPFC of subjects with AD or MDD. These genes play important roles in the nervous system and the innate immune system. Furthermore, we found HSPG2, DAB2IP, ARHGAP22, TXNRD1, MYO10, SDK1 and KRT82 as common differentially methylated genes in the DLPFC of cases with AD or MDD. Finally, as evidence of shared molecular mechanisms behind this comorbidity, we propose some genes as candidate biomarkers for both AD and MDD. However, more research is required to clarify the molecular mechanisms underlying the co-existence of these two important neuropsychiatric disorders.