Aberrantly methylated-differentially expressed genes and pathways in colorectal cancer

Abstract Background Methylation plays an important role in the etiology and pathogenesis of colorectal cancer (CRC). This study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) and pathways in CRC by comprehensive bioinformatics analysis. Methods Data of gene expression...

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Main Authors: Jingwei Liu, Hao Li, Liping Sun, Zhenning Wang, Chengzhong Xing, Yuan Yuan
Format: Article
Language:English
Published: BMC 2017-08-01
Series:Cancer Cell International
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12935-017-0444-4
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author Jingwei Liu
Hao Li
Liping Sun
Zhenning Wang
Chengzhong Xing
Yuan Yuan
author_facet Jingwei Liu
Hao Li
Liping Sun
Zhenning Wang
Chengzhong Xing
Yuan Yuan
author_sort Jingwei Liu
collection DOAJ
description Abstract Background Methylation plays an important role in the etiology and pathogenesis of colorectal cancer (CRC). This study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) and pathways in CRC by comprehensive bioinformatics analysis. Methods Data of gene expression microarrays (GSE68468, GSE44076) and gene methylation microarrays (GSE29490, GSE17648) were downloaded from GEO database. Aberrantly methylated-DEGs were obtained by GEO2R. Functional and enrichment analyses of selected genes were performed using DAVID database. Protein–protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. MCODE was used for module analysis of the PPI network. Results Totally 411 hypomethylation-high expression genes were identified, which were enriched in biological processes of response to wounding or inflammation, cell proliferation and adhesion. Pathway enrichment showed cytokine–cytokine receptor interaction, p53 signaling and cell cycle. The top 5 hub genes of PPI network were CAD, CCND1, ATM, RB1 and MET. Additionally, 239 hypermethylation-low expression genes were identified, which demonstrated enrichment in biological processes including cell–cell signaling, nerve impulse transmission, etc. Pathway analysis indicated enrichment in calcium signaling, maturity onset diabetes of the young, cell adhesion molecules, etc. The top 5 hub genes of PPI network were EGFR, ACTA1, SST, ESR1 and DNM2. After validation in TCGA database, most hub genes still remained significant. Conclusion In summary, our study indicated possible aberrantly methylated-differentially expressed genes and pathways in CRC by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of CRC. Hub genes including CAD, CCND1, ATM, RB1, MET, EGFR, ACTA1, SST, ESR1 and DNM2 might serve as aberrantly methylation-based biomarkers for precise diagnosis and treatment of CRC in the future.
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spelling doaj.art-06dd243ca8c5439b975286d983c791e42022-12-22T01:54:14ZengBMCCancer Cell International1475-28672017-08-0117111010.1186/s12935-017-0444-4Aberrantly methylated-differentially expressed genes and pathways in colorectal cancerJingwei Liu0Hao Li1Liping Sun2Zhenning Wang3Chengzhong Xing4Yuan Yuan5Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education DepartmentTumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education DepartmentTumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education DepartmentTumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education DepartmentTumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education DepartmentTumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education DepartmentAbstract Background Methylation plays an important role in the etiology and pathogenesis of colorectal cancer (CRC). This study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) and pathways in CRC by comprehensive bioinformatics analysis. Methods Data of gene expression microarrays (GSE68468, GSE44076) and gene methylation microarrays (GSE29490, GSE17648) were downloaded from GEO database. Aberrantly methylated-DEGs were obtained by GEO2R. Functional and enrichment analyses of selected genes were performed using DAVID database. Protein–protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. MCODE was used for module analysis of the PPI network. Results Totally 411 hypomethylation-high expression genes were identified, which were enriched in biological processes of response to wounding or inflammation, cell proliferation and adhesion. Pathway enrichment showed cytokine–cytokine receptor interaction, p53 signaling and cell cycle. The top 5 hub genes of PPI network were CAD, CCND1, ATM, RB1 and MET. Additionally, 239 hypermethylation-low expression genes were identified, which demonstrated enrichment in biological processes including cell–cell signaling, nerve impulse transmission, etc. Pathway analysis indicated enrichment in calcium signaling, maturity onset diabetes of the young, cell adhesion molecules, etc. The top 5 hub genes of PPI network were EGFR, ACTA1, SST, ESR1 and DNM2. After validation in TCGA database, most hub genes still remained significant. Conclusion In summary, our study indicated possible aberrantly methylated-differentially expressed genes and pathways in CRC by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of CRC. Hub genes including CAD, CCND1, ATM, RB1, MET, EGFR, ACTA1, SST, ESR1 and DNM2 might serve as aberrantly methylation-based biomarkers for precise diagnosis and treatment of CRC in the future.http://link.springer.com/article/10.1186/s12935-017-0444-4MethylationExpressionBioinformaticsColorectal cancer
spellingShingle Jingwei Liu
Hao Li
Liping Sun
Zhenning Wang
Chengzhong Xing
Yuan Yuan
Aberrantly methylated-differentially expressed genes and pathways in colorectal cancer
Cancer Cell International
Methylation
Expression
Bioinformatics
Colorectal cancer
title Aberrantly methylated-differentially expressed genes and pathways in colorectal cancer
title_full Aberrantly methylated-differentially expressed genes and pathways in colorectal cancer
title_fullStr Aberrantly methylated-differentially expressed genes and pathways in colorectal cancer
title_full_unstemmed Aberrantly methylated-differentially expressed genes and pathways in colorectal cancer
title_short Aberrantly methylated-differentially expressed genes and pathways in colorectal cancer
title_sort aberrantly methylated differentially expressed genes and pathways in colorectal cancer
topic Methylation
Expression
Bioinformatics
Colorectal cancer
url http://link.springer.com/article/10.1186/s12935-017-0444-4
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AT haoli aberrantlymethylateddifferentiallyexpressedgenesandpathwaysincolorectalcancer
AT lipingsun aberrantlymethylateddifferentiallyexpressedgenesandpathwaysincolorectalcancer
AT zhenningwang aberrantlymethylateddifferentiallyexpressedgenesandpathwaysincolorectalcancer
AT chengzhongxing aberrantlymethylateddifferentiallyexpressedgenesandpathwaysincolorectalcancer
AT yuanyuan aberrantlymethylateddifferentiallyexpressedgenesandpathwaysincolorectalcancer