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pmid:32058995
Identification of Hub Genes and Pathways in Gastric Adenocarcinoma Based on Bioinformatics Analysis.
Jieping Qiu · Mengyu Sun · Yaoqun Wang · Bo Chen
Medical science monitor : international medical journal of experimental and clinical research · 2020 doi:10.12659/MSM.920261
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Complete file
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The purpose of this research was to identify differentially expressed genes (DEGs) of gastric adenocarcinoma by use of bioinformatics methods. MATERIAL AND METHODS The gene microarray datasets of GSE103236, GSE79973, and GSE29998 were imported from the GEO database, containing 70 gastric adenocarcinoma samples and 68 matched normal samples. Gene ontology (GO) and KEGG analysis were applied to screened DEGs; Cytoscape software was used for constructing protein-protein interaction (PPI) networks and to perform module analysis of the DEGs. UALCAN was used for prognostic analysis. RESULTS We identified 2909 upregulated DEGs (uDEGs) and 7106 downregulated DEGs (dDEGs) of gastric adenocarcinoma. The GO analysis showed uDEGs were enriched in skeletal system development, cell adhesion, and biological adhesion. KEGG pathway analysis showed uDEGs were enriched in ECM-receptor interaction, focal adhesion, and Cytokine-cytokine receptor interaction. The top 10 hub genes - COL1A1, COL3A1, COL1A2, BGN, COL5A2, THBS2, TIMP1, SPP1, PDGFRB, and COL4A1 - were distinguished from the PPI network. These 10 hub genes were shown to be significantly upregulated in gastric adenocarcinoma tissues in GEPIA. Prognostic analysis of the 10 hub genes via UALCAN showed that the upregulated expression of COL3A1, COL1A2, BGN, and THBS2 significantly reduced the survival time of gastric adenocarcinoma patients. Module analysis revealed that gastric adenocarcinoma was related to 2 pathways: including focal adhesion signaling and ECM-receptor interaction. CONCLUSIONS This research distinguished hub genes and relevant signal pathways, which contributes to our understanding of the molecular mechanisms, and could be used as diagnostic indicators and therapeutic biomarkers for gastric adenocarcinoma.", "claims": [{"id": "claim-method", "statement": "The data were divided into a gastric adenocarcinoma group and a normal group for further analysis by GEO2R.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32058995", "locator": "sections[4] \"Data processing\" paragraph 2", "quote": "The data were divided into a gastric adenocarcinoma group and a normal group for further analysis by GEO2R."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE103236 contains 19 samples, including 10 gastric adenocarcinoma samples and 9 matched normal mucosa samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32058995", "locator": "sections[3] \"Datasets\" paragraph 2", "quote": "GSE103236 contains 19 samples, including 10 gastric adenocarcinoma samples and 9 matched normal mucosa samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32058995"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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TOX, GCNT2, SST, PLCXD3, XYLT2, SLC6A16, CWH43, PDK4, GFRA2, GPR155, GREM2, NR3C2, PLA2G1B, MUC6, LINGO2, RNASE1, MYZAP, GUCA1C, AKR1C1, ACACB, PNPLA7, FXYD1, BAALC, PPP2R3A, BMP5, CKM, FBXL13, COBLL1, RGMB, FBP2, FAM150B, HIF3A, GSTA4, FGG, CHGA, RAB26, CAPN9, MT1M, SGSM1, ASPA, SCGN, SULT2A1, GAMT, CDHR3, CCKBR, ADRB2, GRIA3, SCGB2A1, SLC7A8, DUOX1, SORCS1, ARHGEF37, SCARA5, PACSIN1, LIFR, FNDC5, GLUL, CHIA, METTL7A, FAM189A2, SSTR1, PAIP2B, ACER2, ADH1B, MYRIP, KCNE2, PPP1R3C, TCEA3, PDE8B, SIGLEC11, KBTBD12"]], "row_count": 3, "column_count": 3, "numeric_cells": 4, "header_rows": 1, "locator": "section[9]/table-wrap[1]#t1-medscimonit-26-e920261"}}, {"id": "asset:table:pmid:32058995:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:488171f4b74c285b7339b52ca757f468dec53e14b80b59cc0b0397f53b82c865", "bytes": 5784, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#t2-medscimonit-26-e920261", "version": null, "note": "Gene ontology analysis of DEGs related to gastric adenocarcinoma.", "structure": {"pmcid": "PMC7034404", "section_index": 10, "section_title": "GO term enrichment analysis", "row_count": 55, "column_count": 7}, "table": {"label": "Table 2", "caption": "Gene ontology analysis of DEGs related to gastric adenocarcinoma.", "rows": [["Expression", "Category", "Term", "Count", "%", "P value", "FDR"], ["Upregulated", "GOTERM_BP_FAT", "GO: 0001501~skeletal system development", "19", "3.140495868", "6.25E-17", "1.67E-13"], ["GOTERM_BP_FAT", "GO: 0007155~cell adhesion", "20", "3.305785124", "4.39E-12", "6.55E-09"], ["GOTERM_BP_FAT", "GO: 0022610~biological adhesion", "20", "3.305785124", "4.50E-12", "6.72E-09"], ["GOTERM_BP_FAT", "GO: 0030199~collagen fibril organization", "8", "1.32231405", "1.19E-11", "1.78E-08"], ["GOTERM_BP_FAT", "GO: 0030198~extracellular matrix organization", "8", "1.32231405", "1.30E-07", "1.95E-04"], ["GOTERM_BP_FAT", "GO: 0001503~ossification", "8", "1.32231405", "2.60E-07", "3.89E-04"], ["GOTERM_BP_FAT", "GO: 0060348~bone development", "8", "1.32231405", "4.12E-07", "6.16E-04"], ["GOTERM_BP_FAT", "GO: 0043062~extracellular structure organization", "8", "1.32231405", "2.75E-06", "0.0041046"], ["GOTERM_BP_FAT", "GO: 0032963~collagen metabolic process", "5", "0.826446281", "3.71E-06", "0.005542186"], ["GOTERM_BP_FAT", "GO: 0043588~skin development", "5", "0.826446281", "4.29E-06", "0.006410681"], ["GOTERM_CC_FAT", "GO: 0005578~proteinaceous extracellular matrix", "25", "4.132231405", "1.86E-24", "2.10E-21"], ["GOTERM_CC_FAT", "GO: 0031012~extracellular matrix", "25", "4.132231405", "1.14E-23", "1.28E-20"], ["GOTERM_CC_FAT", "GO: 0005576~extracellular region", "40", "6.611570248", "6.86E-20", "7.75E-17"], ["GOTERM_CC_FAT", "GO: 0044421~extracellular region part", "30", "4.958677686", "8.27E-19", "9.34E-16"], ["GOTERM_CC_FAT", "GO: 0044420~extracellular matrix part", "14", "2.314049587", "1.64E-15", "1.88E-12"], ["GOTERM_CC_FAT", "GO: 0005581~collagen", "9", "1.487603306", "1.49E-12", "1.68E-09"], ["GOTERM_CC_FAT", "GO: 0005583~fibrillar collagen", "5", "0.826446281", "1.48E-07", "1.67E-04"], ["GOTERM_CC_FAT", "GO: 0005604~basement membrane", "6", "0.991735537", "2.04E-05", "0.023013251"], ["GOTERM_CC_FAT", "GO: 0031093~platelet alpha granule lumen", "5", "0.826446281", "2.76E-05", "0.031185256"], ["GOTERM_CC_FAT", "GO: 0060205~cytoplasmic membrane-bounded vesicle lumen", "5", "0.826446281", "3.67E-05", "0.041403378"], ["GOTERM_MF_FAT", "GO: 0005201~extracellular matrix structural constituent", "11", "1.818181818", "5.06E-13", "5.90E-10"], ["GOTERM_MF_FAT", "GO: 0005198~structural molecule activity", "14", "2.314049587", "3.15E-07", "3.67E-04"], ["GOTERM_MF_FAT", "GO: 0005518~collagen binding", "5", "0.826446281", "8.88E-06", "0.010355681"], ["GOTERM_MF_FAT", "GO: 0005539~glycosaminoglycan binding", "7", "1.157024793", "1.19E-05", "0.013923194"], ["GOTERM_MF_FAT", "GO: 0001871~pattern binding", "7", "1.157024793", "2.05E-05", "0.023961179"], ["GOTERM_MF_FAT", "GO: 0030247~polysaccharide binding", "7", "1.157024793", "2.05E-05", "0.023961179"], ["GOTERM_MF_FAT", "GO: 0008201~heparin binding", "6", "0.991735537", "3.72E-05", "0.043401787"], ["GOTERM_MF_FAT", "GO: 0050840~extracellular matrix binding", "4", "0.661157025", "1.30E-04", "0.151895387"], ["GOTERM_MF_FAT", "GO: 0005509~calcium ion binding", "12", "1.983471074", "4.20E-04", "0.488103889"], ["GOTERM_MF_FAT", "GO: 0008237~metallopeptidase activity", "6", "0.991735537", "5.52E-04", "0.641829759"], ["Downregulated", "GOTERM_BP_FAT", "GO: 0007586~digestion", "12", "1.038062284", "7.45E-12", "1.09E-08"], ["GOTERM_BP_FAT", "GO: 0055114~oxidation reduction", "15", "1.297577855", "3.07E-05", "0.045029161"], ["GOTERM_BP_FAT", "GO: 0006081~cellular aldehyde metabolic process", "4", "0.346020761", "6.53E-04", "0.952399247"], ["GOTERM_BP_FAT", "GO: 0030001~metal ion transport", "10", "0.865051903", "0.00213818", "3.08666015"], ["GOTERM_BP_FAT", "GO: 0006812~cation transport", "10", "0.865051903", "0.006666616", "9.333089916"], ["GOTERM_BP_FAT", "GO: 0006811~ion transport", "12", "1.038062284", "0.007065784", "9.865306976"], ["GOTERM_BP_FAT", "GO: 0046903~secretion", "7", "0.605536332", "0.010249221", "14.00683938"], ["GOTERM_BP_FAT", "GO: 0015672~monovalent inorganic cation transport", "7", "0.605536332", "0.01337189", "17.89646714"], ["GOTERM_BP_FAT", "GO: 0006813~potassium ion transport", "5", "0.432525952", "0.016821807", "22.00279704"], ["GOTERM_BP_FAT", "GO: 0022600~digestive system process", "3", "0.259515571", "0.018374485", "23.78773935"], ["GOTERM_CC_FAT", "GO: 0005576~extracellular region", "31", "2.6816609", "1.26E-05", "0.014253173"], ["GOTERM_CC_FAT", "GO: 0045177~apical part of cell", "7", "0.605536332", "0.001371031", "1.545706714"], ["GOTERM_CC_FAT", "GO: 0016324~apical plasma membrane", "6", "0.519031142", "0.002113034", "2.373127171"], ["GOTERM_CC_FAT", "GO: 0005624~membrane fraction", "11", "0.951557093", "0.047644803", "42.55171216"], ["GOTERM_MF_FAT", "GO: 0031420~alkali metal ion binding", "7", "0.605536332", "0.004013875", "5.198242704"], ["GOTERM_MF_FAT", "GO: 0004033~aldo-keto reductase activity", "3", "0.259515571", "0.004305787", "5.566366984"], ["GOTERM_MF_FAT", "GO: 0004198~calcium-dependent cysteine-type endopeptidase activity", "3", "0.259515571", "0.004899806", "6.31139254"], ["GOTERM_MF_FAT", "GO: 0008289~lipid binding", "9", "0.778546713", "0.009796998", "12.2496158"], ["GOTERM_MF_FAT", "GO: 0016620~oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor", "3", "0.259515571", "0.010025001", "12.51741656"], ["GOTERM_MF_FAT", "GO: 0030955~potassium ion binding", "5", "0.432525952", "0.010277041", "12.81257072"], ["GOTERM_MF_FAT", "GO: 0008233~peptidase activity", "10", "0.865051903", "0.013517076", "16.52574449"], ["GOTERM_MF_FAT", "GO: 0015267~channel activity", "8", "0.692041522", "0.019316845", "22.80964632"], ["GOTERM_MF_FAT", "GO: 0022803~passive transmembrane transporter activity", "8", "0.692041522", "0.01954695", "23.04969236"], ["GOTERM_MF_FAT", "GO: 0008900~hydrogen: potassium-exchanging ATPase activity", "2", "0.173010381", "0.019742308", "23.25294859"]], "row_count": 55, "column_count": 7, "numeric_cells": 270, "header_rows": 1, "locator": "section[10]/table-wrap[1]#t2-medscimonit-26-e920261"}}, {"id": "asset:table:pmid:32058995:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:15af2e14966e65e06014d3fd8192675b3b62fad37c7579b4c39bde7e34f9b1f1", "bytes": 1056, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#t3-medscimonit-26-e920261", "version": null, "note": "KEGG pathway analysis of DEGs associated with gastric adenocarcinoma.", "structure": {"pmcid": "PMC7034404", "section_index": 11, "section_title": "KEGG signal pathway analysis", "row_count": 10, "column_count": 6}, "table": {"label": "Table 3", "caption": "KEGG pathway analysis of DEGs associated with gastric adenocarcinoma.", "rows": [["Expression", "Term", "Count", "%", "P value", "FDR"], ["Upregulated", "hsa04512: ECM-receptor interaction", "11", "1.818181818", "2.66E-13", "2.14E-10"], ["hsa04510: Focal adhesion", "11", "1.818181818", "1.80E-09", "1.44E-06"], ["hsa04350: TGF-beta signaling pathway", "4", "0.661157025", "0.005149174", "4.056689024"], ["Downregulated", "hsa00982: Drug metabolism", "8", "0.692041522", "1.46E-07", "1.41E-04"], ["hsa00830: Retinol metabolism", "7", "0.605536332", "1.38E-06", "0.001338048"], ["hsa00980: Metabolism of xenobiotics by cytochrome P450", "7", "0.605536332", "2.60E-06", "0.002518197"], ["hsa00010: Glycolysis/Gluconeogenesis", "4", "0.346020761", "0.007818033", "7.311759835"], ["hsa00591: Linoleic acid metabolism", "3", "0.259515571", "0.015552893", "14.070282"], ["hsa00350: Tyrosine metabolism", "3", "0.259515571", "0.036348334", "30.10544025"]], "row_count": 10, "column_count": 6, "numeric_cells": 45, "header_rows": 1, "locator": "section[11]/table-wrap[1]#t3-medscimonit-26-e920261"}}, {"id": "asset:table:pmid:32058995:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d1a1f89c744662e5e1f505771fcad971687f4aaa0004bffd55aba2cf766459d6", "bytes": 788, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#t4-medscimonit-26-e920261", "version": null, "note": "Connectivity and regulation of the top 10 hub genes.", "structure": {"pmcid": "PMC7034404", "section_index": 12, "section_title": "PPI network construction, module analysis and hub genes determination", "row_count": 11, "column_count": 4}, "table": {"label": "Table 4", "caption": "Connectivity and regulation of the top 10 hub genes.", "rows": [["Gene symbol", "Gene title", "Connectivity", "Regulation"], ["COL1A1", "Collagen type I alpha 1 chain", "34", "Up"], ["COL3A1", "Collagen type III alpha 1 chain", "30", "Up"], ["COL1A2", "Collagen type I alpha 2 chain", "29", "Up"], ["BGN", "Biglycan", "29", "Up"], ["COL5A2", "Collagen type V alpha 2 chain", "23", "Up"], ["THBS2", "Thrombospondin 2", "23", "Up"], ["TIMP1", "TIMP metallopeptidase inhibitor 1", "21", "Up"], ["SPP1", "Secreted phosphoprotein 1", "20", "Up"], ["PDGFRB", "Platelet-derived growth factor receptor beta", "20", "Up"], ["COL4A1", "Collagen type IV alpha 1 chain", "19", "Up"]], "row_count": 11, "column_count": 4, "numeric_cells": 18, "header_rows": 1, "locator": "section[12]/table-wrap[1]#t4-medscimonit-26-e920261"}}], "gaps": ["asset:data:geo:GSE103236 not downloaded", "asset:data:geo:GSE103236 licence not read", "asset:data:geo:GSE29998 not downloaded", "asset:data:geo:GSE29998 licence not read", 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