Identification of DNA methylation associated gene signatures in endometrial cancer via integrated analysis of DNA methylation and gene expression systematically

Abstract

ObjectiveEndometrial cancer (EC) is a common gynecologic cancer worldwide. However, the pathogenesis of EC has not been epigenetically elucidated. Here, this study aims to describe the DNA methylation profile and identify favorable gene signatures highly associated with aberrant DNA methylation changes in EC.MethodsThe data regarding DNA methylation and gene expression were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially methylated CpG sites (DMCs), differentially methylated regions (DMRs), and differentially expressed genes (DEGs) were identified, and the relationship between the 2 omics was further analyzed. In addition, weighted CpG site co-methylation network (WCCN) was constructed followed by an integrated analysis of DNA methylation and gene expression data.ResultsFour hundred thirty-one tumor tissues and 46 tissues adjacent tumor of EC patients were analyzed. One thousand one hundred thirty-five DMCs (merging to 10 DMRs), and 1,488 DEGs were obtained between tumor and normal groups, respectively. One hundred forty-eight DMCs-DEGs correlated pairs and 13 regional DMCs-DEGs pairs were obtained. Interestingly, we found that some hub genes in 2 modules among 8 modules of WCCN analysis were down-regulated in tumor samples. Furthermore, protocadherins (PCDHs) clusters, DDP6, TNXB, and ZNF154 were identified as novel deregulated genes with altered methylation in EC.ConclusionBased on the analysis of DNA methylation in a systematic view, the potential long-range epigenetic silencing (LRES) composed of PCDHs was reported in ECs for the first time. PCDHs clusters, DDP6, and TNXB were firstly found to be associated with tumorigenesis, and may be novel candidate biomarkers for EC.

A functional variant in TNXB promoter associates with the risk of esophageal squamous‐cell carcinoma

“…Previous studies reported that TNXB was important for the tumorigenesis of lung adenocarcinoma 36 and identified TNXB as a novel deregulated gene with altered methylation in endometrial cancer. 25 In this study, we demonstrated that TNXB mRNA expression was downregulated in ESCC compared with adjacent normal tissues.…”

“…However, the role of TNXB in tumorigenesis has not been well characterized. Previous studies reported that TNXB was important for the tumorigenesis of lung adenocarcinoma 36 and identified TNXB as a novel deregulated gene with altered methylation in endometrial cancer 25 …”

“…Very little is known about the mechanism relevance of this gene to tumor development. Men et al 25 demonstrated that TNXB mapped in pathways of focal adhesion, ECM receptor interaction, and calcium signaling pathway. Sanchez‐Antolín et al 37 previously reported that TNXB affected the activation of the TGF‐β signaling, and TGF‐β could interact with the PI3K‐Akt signaling, potentially 38 .…”

“…TNXB encodes tenascin‐X, a member of the tenascin family of extracellular matrix (ECM) glycoproteins that is involved in collagen organization and matrix integrity 20‐22 . TNXB has been reported to have altered expression in several types of cancer 23‐27 but little was known about its role in esophageal tumorigenesis.…”

“…involved in collagen organization and matrix integrity. [20][21][22] TNXB has been reported to have altered expression in several types of cancer [23][24][25][26][27] but little was known about its role in esophageal tumorigenesis.…”