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pmid:28794688
Aberrantly methylated-differentially expressed genes and pathways in colorectal cancer.
Jingwei Liu · Hao Li · Liping Sun · Zhenning Wang · Chengzhong Xing · Yuan Yuan
Cancer cell international · 2017 doi:10.1186/s12935-017-0444-4
Paper
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Experiment
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Data
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Analysis
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Execution
absent
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Complete file
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This study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) and pathways in CRC by comprehensive bioinformatics analysis.\nMETHODS: 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.\nRESULTS: 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.\nCONCLUSION: 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. 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status", "P value"], ["Hypomethylation and high expression"], ["", "CAD", "Hypomethylation", "5.55E−16", "Up-regulated", "3.88E−18"], ["", "CCND1", "Hypomethylation", "0.032", "Up-regulated", "7.26E−17"], ["", "ATM", "–", "–", "Up-regulated", "0.006"], ["", "RB1", "Hypomethylation", "5.27E−03", "Up-regulated", "1.17E−11"], ["", "DNM2", "Hypomethylation", "1.36E−13", "Up-regulated", "5.23E−08"], ["Hypermethylation and low expression"], ["", "EGFR", "Hypermethylation", "4.65E−14", "Down-regulated", "7.20E−21"], ["", "ACTA1", "Hypermethylation", "1.64E−14", "–", "–"], ["", "SST", "Hypermethylation", "9.67E−14", "Down-regulated", "2.22E−31"], ["", "ESR1", "Hypermethylation", "1.18E−14", "Down-regulated", "9.62E−20"], ["", "DNM2", "Hypermethylation", "5.43E−06", "–", "–"]], "row_count": 13, "column_count": 6, "numeric_cells": 17, "header_rows": 1, "locator": "section[13]/table-wrap[1]#Tab4"}}, {"id": "asset:table:pmid:28794688:2", "role": "table", "format": "jats-table", "media_type": 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"GOTERM_BP_FAT", "GO:0008283~cell proliferation", "29", "7.06", "7.95E−06"], ["", "GOTERM_BP_FAT", "GO:0007155~cell adhesion", "37", "9.00", "5.54E−05"], ["", "GOTERM_BP_FAT", "GO:0022610~biological adhesion", "37", "9.00", "5.55E−05"], ["", "GOTERM_CC_FAT", "GO:0005576~extracellular region", "92", "22.38", "2.01E−08"], ["", "GOTERM_CC_FAT", "GO:0044421~extracellular region part", "55", "13.38", "3.78E−08"], ["", "GOTERM_CC_FAT", "GO:0005615~extracellular space", "42", "10.22", "4.12E−07"], ["", "GOTERM_CC_FAT", "GO:0005578~proteinaceous extracellular matrix", "21", "5.11", "2.45E−04"], ["", "GOTERM_CC_FAT", "GO:0005625~soluble fraction", "20", "4.87", "5.01E−04"], ["", "GOTERM_MF_FAT", "GO:0042802~identical protein binding", "35", "8.52", "8.25E−05"], ["", "GOTERM_MF_FAT", "GO:0005125~cytokine activity", "15", "3.65", "6.69E−04"], ["", "GOTERM_MF_FAT", "GO:0004175~endopeptidase activity", "21", "5.11", "2.33E−03"], ["", "GOTERM_MF_FAT", "GO:0030674~protein binding, bridging", "9", "2.19", "3.39E−03"], ["", "GOTERM_MF_FAT", "GO:0008201~heparin binding", "9", "2.19", "5.90E−03"], ["Hypermethylation and low expression"], ["", "GOTERM_BP_FAT", "GO:0007267~cell–cell signaling", "29", "12.13", "3.32E−07"], ["", "GOTERM_BP_FAT", "GO:0019226~transmission of nerve impulse", "18", "7.53", "4.70E−05"], ["", "GOTERM_BP_FAT", "GO:0031644~regulation of neurological system process", "11", "4.60", "1.72E−04"], ["", "GOTERM_BP_FAT", "GO:0007610~behavior", "20", "8.37", "1.90E−04"], ["", "GOTERM_BP_FAT", "GO:0030182~neuron differentiation", "19", "7.95", "2.35E−04"], ["", "GOTERM_CC_FAT", "GO:0044459~plasma membrane part", "64", "26.78", "2.13E−09"], ["", "GOTERM_CC_FAT", "GO:0005886~plasma membrane", "84", "35.15", "5.38E−07"], ["", "GOTERM_CC_FAT", "GO:0043005~neuron projection", "19", "7.95", "1.13E−06"], ["", "GOTERM_CC_FAT", "GO:0005887~integral to plasma membrane", "38", "15.90", "1.67E−06"], ["", "GOTERM_CC_FAT", "GO:0031226~intrinsic to plasma membrane", "38", "15.90", "2.85E−06"], ["", "GOTERM_MF_FAT", "GO:0003700~transcription factor activity", "38", "15.90", "2.48E−07"], ["", "GOTERM_MF_FAT", "GO:0022836~gated channel activity", "16", "6.69", "9.15E−05"], ["", "GOTERM_MF_FAT", "GO:0015267~channel activity", "18", "7.53", "2.17E−04"], ["", "GOTERM_MF_FAT", "GO:0022803~passive transmembrane transporter activity", "18", "7.53", "2.23E−04"], ["", "GOTERM_MF_FAT", "GO:0005216~ion channel activity", "17", "7.11", "3.17E−04"]], "row_count": 33, "column_count": 6, "numeric_cells": 120, "header_rows": 1, "locator": "section[10]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:28794688:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cd134a2b3300a6669fcb41788f2ac574d8f1dcaff21265aeed3f2ed877bda71a", "bytes": 1615, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[2]#Tab2", "version": null, "note": "KEGG pathway analysis of aberrantly methylated-differentially expressed genes in colorectal cancer", "structure": {"pmcid": "PMC5545832", "section_index": 10, "section_title": "GO functional enrichment analysis", "row_count": 12, "column_count": 6}, "table": {"label": "Table 2", "caption": "KEGG pathway analysis of aberrantly methylated-differentially expressed genes in colorectal cancer", "rows": [["Pathway ID", "Pathway name", "Gene no.", "%", "P value", "Genes"], ["Hypomethylation and high expression"], ["hsa04060", "Cytokine–cytokine receptor interaction", "20", "4.87", "5.86E−04", "CXCL1, IL2RA, LTBR, CXCL3, IL21R, CXCL2, MET, CXCL9, TNFSF15, TNFRSF4, CCL18, LIF, INHBA, TNFRSF9, TNFSF11, IL23A, PRLR, CCL20, IL20RA, ACVR1"], ["hsa04115", "p53 signaling pathway", "8", "1.95", "5.54E−03", "CCND1, SERPINB5, CD82, RRM2, TSC2, CASP8, PMAIP1, ATM"], ["hsa04110", "Cell cycle", "9", "2.19", "0.045", "CCND1, PKMYT1, PRKDC, RB1, CDC16, CDC27, ATM, WEE1, TFDP1"], ["Hypermethylation and low expression"], ["hsa04020", "Calcium signaling pathway", "12", "5.02", "7.80E−04", "EGFR, EDNRB, ADCY2, PTGER3, PDE1B, PDE1C, DRD5, GRIN2A, PLCD1, ITPKB, CAMK2B, PTGFR"], ["hsa04950", "Maturity onset diabetes of the young", "5", "2.09", "1.45E−03", "HHEX, NEUROD1, HNF4G, NEUROG3, NKX2-2"], ["hsa04514", "Cell adhesion molecules (CAMs)", "8", "3.35", "0.017", "NCAM1, CD8A, ITGA8, NLGN4X, CNTN1, ITGA4, JAM2, HLA-G"], ["hsa04080", "Neuroactive ligand-receptor interaction", "11", "4.60", "0.033", "EDNRB, SSTR2, PTGER3, GABRB3, GRIK1, GRIK2, DRD5, GRIN2A, GRIA3, PTGFR, VIPR2"], ["hsa04062", "Chemokine signaling pathway", "9", "3.77", "0.035", "DOCK2, ADCY2, CXCL14, TIAM1, HCK, PIK3CD, CCR10, RAP1A, ELMO1"], ["hsa04666", "Fc gamma R-mediated phagocytosis", "6", "2.51", "0.043", "DOCK2, HCK, PIK3CD, ARF6, AMPH, DNM2"]], "row_count": 12, "column_count": 6, "numeric_cells": 42, "header_rows": 1, "locator": "section[10]/table-wrap[2]#Tab2"}}, {"id": "asset:table:pmid:28794688:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:bb4cd6a79a63adf8db5840c4ee91f6ce0e840cc81f2859c31a9761e79993bd21", "bytes": 1330, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab3", "version": null, "note": "Module analysis of the protein–protein interaction network", "structure": {"pmcid": "PMC5545832", "section_index": 12, "section_title": "PPI network construction, module analysis and hub gene selection", "row_count": 13, "column_count": 6}, "table": {"label": "Table 3", "caption": "Module analysis of the protein–protein interaction network", "rows": [["Category", "Module", "Function description", "FDR", "Nodes", "Genes"], ["Hypomethylation and high expression"], ["", "1", "Chemokine signaling pathway", "1.14E−10", "6", "CCL18, CXCL2, CXCL1, CCL20, CXCL9, CXCL3"], ["", "2", "Ribosome", "6.80E−04", "5", "RPL31, PABPC1, UPF3A, RPS15A, RPS15"], ["", "3", "Nucleic acid binding", "0.0195", "9", "DDX49, AHR, GSTP1, RB1, AATF, DDX56, NOC2L, IMP4, DDX52"], ["", "4", "Carbon metabolism", "3.43E−04", "5", "GNPDA1, PFKM, ENO1, ME1, HK3"], ["", "5", "Cell cycle", "3.01E−10", "8", "CDC16, PKMYT1, CDC27, TFDP1, SMARCAL1, ATM, RECQL5, WEE1"], ["", "6", "Proteasome", "0.0344", "8", "FGFR1, SOX9, PSMD6, FOXD1, CCND1, MSX1, PSMF1, FOXA2"], ["Hypermethylation and low expression"], ["", "1", "Synaptic transmission", "1.04E−07", "7", "KCND3, KCNG1, KCNB1, HCN2, KCNK3, KCNA5, KCNA3"], ["", "2", "Gastric acid secretion", "2.19E−04", "6", "SST, NPY, SSTR2, CCR10, PTGER3, ADCY2"], ["", "3", "Glutamatergic synapse", "1.09E−06", "5", "GRIK1, GRIK2, GRIA3, GRIN2A, CAMK2B"], ["", "4", "Cell fate specification", "9.20E−03", "15", "ARHGEF16, RHOH, TIAM1, ABR, RAP1A, NEUROD1, AR, ESR1, EGFR, TF, FEV, INPP5B, SOX17, FGD2, NKX2-2"]], "row_count": 13, "column_count": 6, "numeric_cells": 36, "header_rows": 1, "locator": 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