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

Objective Endometrial 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. Methods The 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. Results Four 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. Conclusion Based 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.

• Publication year

  2017

• Venue

  Journal of Gynecologic Oncology

• Publication date

  2017-07-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3802/jgo.2017.28.e83PMID 29027401PMCID 5641533
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• COHCAP: an integrative genomic pipeline for single-nucleotide resolution DNA methylation analysis

  2019cited by this paper
• Identification of endometrial cancer methylation features using combined methylation analysis methods

  2017cited by this paper
• Molecular approaches for classifying endometrial carcinoma.

  2017cited by this paper
• DNA methylation promotes paired box 2 expression via myeloid zinc finger 1 in endometrial cancer

  2016cited by this paper
• Integrated Epigenomics Analysis Reveals a DNA Methylation Panel for Endometrial Cancer Detection Using Cervical Scrapings

  2016cited by this paper
• Robust Detection of DNA Hypermethylation of ZNF154 as a Pan-Cancer Locus with in Silico Modeling for Blood-Based Diagnostic Development.

  2016cited by this paper
• AXL modulates extracellular matrix protein expression and is essential for invasion and metastasis in endometrial cancer

  2016cited by this paper
• Differential DNA methylation marks and gene comethylation of COPD in African-Americans with COPD exacerbations

  2016cited by this paper
• Methylation of tumor suppressor gene CDH13 and SHP1 promoters and their epigenetic regulation by the UHRF1/PRMT5 complex in endometrial carcinoma.

  2016cited by this paper
• Triple-layer dissection of the lung adenocarcinoma transcriptome – regulation at the gene, transcript, and exon levels

  2015cited by this paper
• Discovery of Core Biotic Stress Responsive Genes in Arabidopsis by Weighted Gene Co-Expression Network Analysis

  2015cited by this paper
• Quantitative DNA methylation analysis of selected genes in endometrial carcinogenesis.

  2015cited by this paper
• Identification of specific DNA methylation sites on the Y-chromosome as biomarker in prostate cancer

  2015cited by this paper
• qqman: an R package for visualizing GWAS results using Q-Q and manhattan plots

  2014cited by this paper
• Comparative DNA methylome analysis of endometrial carcinoma reveals complex and distinct deregulation of cancer promoters and enhancers

  2014cited by this paper
• Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

  2014cited by this paper
• Recurrent patterns of DNA methylation in the ZNF154, CASP8, and VHL promoters across a wide spectrum of human solid epithelial tumors and cancer cell lines

  2013cited by this paper
• COHCAP: an integrative genomic pipeline for single-nucleotide resolution DNA methylation analysis

  2013cited by this paper
• Genome Wide Analysis of Acute Myeloid Leukemia Reveal Leukemia Specific Methylome and Subtype Specific Hypomethylation of Repeats

  2012cited by this paper
• DNA methylation profiling in the clinic: applications and challenges

  2012cited by this paper
• GeneCodis3: a non-redundant and modular enrichment analysis tool for functional genomics

  2012cited by this paper
• GREAT improves functional interpretation of cis-regulatory regions

  2010cited by this paper
• Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous cell carcinoma

  2010cited by this paper
• Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous cell carcinoma.

  2010cited by this paper
• Original Article Molecular detection of B-cell neoplasms by specific DNA methylation biomarkers

  2010cited by this paper
• Frequent Long-Range Epigenetic Silencing of Protocadherin Gene Clusters on Chromosome 5q31 in Wilms' Tumor

  2009cited by this paper
• WGCNA: an R package for weighted correlation network analysis

  2008cited by this paper
• PCDH8, the human homolog of PAPC, is a candidate tumor suppressor of breast cancer

  2008cited by this paper
• Gene alterations in tumor-associated endothelial cells from endometrial cancer.

  2008cited by this paper
• Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths.

  2008cited by this paper
• Microarray-Based Identification of Tenascin C and Tenascin XB, Genes Possibly Involved in Tumorigenesis Associated with Neurofibromatosis Type 1

  2007cited by this paper
• Large-scale CpG methylation analysis identifies novel candidate genes and reveals methylation hotspots in acute lymphoblastic leukemia.

  2007cited by this paper
• Association of tissue-specific differentially methylated regions (TDMs) with differential gene expression.

  2005cited by this paper
• Epigenetic Silencing of the Protocadherin Family Member PCDH-γ-All in Astrocytomas

  2005cited by this paper
• DNA methylation and human disease

  2005cited by this paper
• Epigenetic silencing of the protocadherin family member PCDH-gamma-A11 in astrocytomas.

  2005cited by this paper
• Cytoscape: a software environment for integrated models of biomolecular interaction networks.

  2003influential reference
• Aberrant CpG-island methylation has non-random and tumour-type–specific patterns

  2000cited by this paper
• Cytosine methylation and the ecology of intragenomic parasites.

  1997cited by this paper

• In vitro assessment of siRNA-mediated LRP5 silencing and temozolomide treatment in glioblastoma and brain cancer stem cells

  2026influential citation
• Molecular dissection of glioblastoma: Identification of prognostic hub genes through integrated bioinformatics analysis

  2026cites this paper
• The Impact of Hydrogen Sulfide Regulatory Gene Alterations on Head and neck squamous cell carcinoma prognosis and tumor microenvironment

  2025influential citation
• SPEF1 and SPEF2 as potential biomarkers in bladder cancer: Insights from a comprehensive bioinformatic analysis

  2025cites this paper
• Aberrant expression of multiple γ-glutamyltransferases is associated with tumor progression and patient outcome in prostate cancers

  2025cites this paper
• Pan-cancer analysis of SOX2: Prognostic implications and potential as a therapeutic target in immune checkpoint modulation

  2025cites this paper
• Mesalazine Regulates DUSP1, DUSP4, and DUSP5 Expression in Colorectal Cancer: In Vitro and Bioinformatic Evidence

  2025cites this paper
• Identification of PPFIA3 as a Potential Prognostic and Immune Biomarker Through Pan‐Cancer Analysis

  2025cites this paper
• Comprehensive analysis identifies endocrine fibroblast growth factors as promising prognostic markers for colorectal carcinoma

  2024cites this paper
• Bioinformatic Analysis of IKK Complex Genes Expression in Selected Gastrointestinal Cancers

  2024influential citation
• Comprehensive pancancer analysis reveals that LPCAT1 is a novel predictive biomarker for prognosis and immunotherapy response

  2024cites this paper
• Analysis of the interlink between glucose-6-phosphate dehydrogenase (G6PD) and lung cancer through multi-omics databases

  2024cites this paper
• Pan-cancer analysis combined with experiments predicts NNMT as a therapeutic target for human cancers

  2024cites this paper
• Pan-cancer analysis predict that FAT1 is a therapeutic target and immunotherapy biomarker for multiple cancer types including non-small cell lung cancer

  2024cites this paper
• The prognostic value and immunological role of MVP in pan-cancer study

  2024influential citation
• Loss of MTAP expression by immunohistochemistry is a surrogate marker for homozygous 9p21.3 deletion in urothelial carcinoma.

  2024cites this paper
• A new methodology to reveal potential nucleic acid modifications associated with the risk of endometrial cancer through dispersive solid-phase extraction coupled with UHPLC-QE-Orbitrap-MS/MS and HPLC–UV

  2024influential citation
• CALML6 as a potential diagnostic marker for thyroid cancer promotes thyroid cancer cell proliferation via modulating the immune microenvironment.

  2024cites this paper
• Expression of ALKBH3 and its effects on proliferation, migration, and invasion of lung adenocarcinoma A549 cells: bioinformatics analysis and in vitro and in vivo experiments

  2024cites this paper
• Integrated pan-cancer analysis and experimental verification of the roles of tropomyosin 4 in gastric cancer

  2023cites this paper
• Identification and Validation of Potentially Clinically Relevant CpG Regions within the Class 2 Tumor Suppressor Gene SFRP1 in Pancreatic Cancer

  2023cites this paper
• CD24-associated ceRNA network reveals prognostic biomarkers in breast carcinoma

  2023cites this paper
• Role of Kinetochore Scaffold 1 (KNL1) in Tumorigenesis and Tumor Immune Microenvironment in Pan-Cancer: Bioinformatics Analyses and Validation of Expression

  2023cites this paper
• Chromatin architectural factor CTCF is essential for progesterone‐dependent uterine maturation

  2023cites this paper
• Epigenetic Status of FBXW7 Gene and Its Role in Ovarian Cancer Pathogenesis

  2023influential citation
• ZNF750: A Novel Prognostic Biomarker in Metastatic Prostate Cancer

  2023cites this paper
• Systematic pan-cancer analysis identifies gasdermin B as an immunological and prognostic biomarker for kidney renal clear cell carcinoma

  2023cites this paper
• Comprehensively prognostic and immunological analysis of VRK Serine/Threonine Kinase 1 in pan-cancer and identification in hepatocellular carcinoma

  2023cites this paper
• Integrated pan-cancer analysis of CSMD2 as a potential prognostic, diagnostic, and immune biomarker

  2022cites this paper
• PAQR5 Expression Is Suppressed by TGFβ1 and Associated With a Poor Survival Outcome in Renal Clear Cell Carcinoma

  2022cites this paper
• Pan-cancer analysis combined with experiments explores the oncogenic role of spindle apparatus coiled-coil protein 1 (SPDL1)

  2022cites this paper
• Liquid Biopsy for Monitoring EC Patients: Towards Personalized Treatment

  2022cites this paper
• Update of gene expression/methylation and MiRNA profiling in colorectal cancer; application in diagnosis, prognosis, and targeted therapy

  2022cites this paper
• Prostanoid Signaling in Cancers: Expression and Regulation Patterns of Enzymes and Receptors

  2022cites this paper
• SOCS3 Acts as an Onco-immunological Biomarker With Value in Assessing the Tumor Microenvironment, Pathological Staging, Histological Subtypes, Therapeutic Effect, and Prognoses of Several Types of Cancer

  2022cites this paper
• Prognostic and Immunotherapeutic Roles of KRAS in Pan-Cancer

  2022cites this paper
• Neuregulin 4 Boosts the Efficacy of Anti-ERBB2 Neutralizing Antibodies

  2022cites this paper
• Integrative Pan-Cancer Analysis Confirmed that FCGR3A is a Candidate Biomarker Associated With Tumor Immunity

  2022cites this paper
• SOCS3 gene silencing does not occur through methylation and mutations in gastric cancer

  2022cites this paper
• Genetic alterations, RNA expression profiling and DNA methylation of HMGB1 in malignancies

  2022cites this paper
• The epiphany derived from T-cell–inflamed profiles: Pan-cancer characterization of CD8A as a biomarker spanning clinical relevance, cancer prognosis, immunosuppressive environment, and treatment responses

  2022cites this paper
• Altered expression of ACOX2 in non-small cell lung cancer

  2022influential citation
• Integrative multi-omics analysis of identified ferroptosis-marker RPL8 as a candidate oncogene correlates with poor prognosis and immune infiltration in liver cancer.

  2022cites this paper
• An integrated pan-cancer analysis of PSAT1: A potential biomarker for survival and immunotherapy

  2022cites this paper
• Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma

  2022cites this paper
• Non-coding ribonucleic acid-mediated CAMSAP1 upregulation leads to poor prognosis with suppressed immune infiltration in liver hepatocellular carcinoma

  2022cites this paper
• A novel family of beta mixture models for the differential analysis of DNA methylation data: An application to prostate cancer

  2022cites this paper
• Comprehensive analysis of the expression and prognosis for APOE in malignancies: A pan-cancer analysis

  2022influential citation
• Multiomics characteristics and immunotherapeutic potential of EZH2 in pan-cancer

  2022cites this paper
• A Risk Score Model Based on Nine Differentially Methylated mRNAs for Predicting Prognosis of Patients with Clear Cell Renal Cell Carcinoma

  2021cites this paper
• circRNA circ_102049 Implicates in Pancreatic Ductal Adenocarcinoma Progression through Activating CD80 by Targeting miR-455-3p

  2021influential citation
• Thorough statistical analyses of breast cancer co-methylation patterns

  2021cites this paper
• High ORAI3 expression correlates with good prognosis in human muscle-invasive bladder cancer.

  2021cites this paper
• MXD3 as an onco-immunological biomarker encompassing the tumor microenvironment, disease staging, prognoses, and therapeutic responses in multiple cancer types

  2021cites this paper
• Disulfiram Improves the Anti-PD-1 Therapy Efficacy by Regulating PD-L1 Expression via Epigenetically Reactivation of IRF7 in Triple Negative Breast Cancer

  2021cites this paper
• m6A Pathway Regulators Are Frequently Mutated in Breast Invasive Carcinoma and May Play an Important Role in Disease Pathogenesis

  2021influential citation
• rs12537 Is a Novel Susceptibility SNP Associated With Estrogen Receptor Positive Breast Cancer in Chinese Han Population

  2021cites this paper
• Hepcidin Downregulation Correlates With Disease Aggressiveness And Immune Infiltration in Liver Cancers

  2021cites this paper
• A comprehensive investigation of m6A regulators prognostic value and associated molecular pathways in breast invasive cancer

  2021cites this paper
• Expression patterns and prognostic value of RUNX genes in kidney cancer

  2021cites this paper
• A ten-DNA methylation signature as a novel biomarker for improving prediction of prognosis and indicating DNA targets in endometrial cancer.

  2021cites this paper
• Identification of Aberrantly Methylated Differentially CpG Sites in Hepatocellular Carcinoma and Their Association With Patient Survival

  2020cites this paper
• Molecular Carcinogenesis

  2020cites this paper
• Establishment and validation of a prognostic nomogram based on a novel five‐DNA methylation signature for survival in endometrial cancer patients

  2020cites this paper
• Differential Wnt-β- catenin pathway activation in HPV positive and negative oral epithelium is transmitted during head and neck tumorigenesis: clinical implications

  2020cites this paper
• Elevated expression of FREM1 in breast cancer indicates favorable prognosis and high‐level immune infiltration status

  2020cites this paper
• Genome and transcriptome profiling of FBXW family in human prostate cancer.

  2020cites this paper
• Analyses of DNA Methylation Involved in the Activation of Nuclear Karyopherin Alpha 2 Leading to Identify the Progression and Prognostic Significance Across Human Breast Cancer

  2020cites this paper
• Frequent promoter methylation of HOXD10 in endometrial carcinoma and its pathological significance.

  2020cites this paper
• Genome-wide characterization of aberrant DNA methylation patterns and the potential clinical implications in patients with endometrial cancer.

  2019cites this paper
• Ranking genomic features using an information-theoretic measure of epigenetic discordance

  2019cites this paper
• Integrative analysis of DNA methylation in discordant twins unveils distinct architectures of systemic sclerosis subsets

  2019cites this paper
• Insight into the Role and Regulation of Gap Junction Genes in Lung Cancer and Identification of Nuclear Cx43 as a Putative Biomarker of Poor Prognosis

  2019cites this paper
• Identification of prognosis markers for endometrial cancer by integrated analysis of DNA methylation and RNA-Seq data

  2019cites this paper
• Limited Role of Promoter Methylation of MGMT and C13ORF18 in Triage of Low-Grade Squamous Intraepithelial Lesion

  2018cites this paper
• into the Role and Regulation of Gap Junction 2 Genes in Lung Cancer and Identification of Nuclear 3 Cx 43 as a Putative Biomarker of Poor Prognosis

  year unknowncites this paper
• Clinicopathological Features, Immune In�ltration Landscape and Involved Signaling Pathways of the desmogleins family in Pancreatic Adenocarcinoma

  year unknowninfluential citation