Screening key genes and signaling pathways in colorectal cancer by integrated bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31173250", "kind": "science-record", "revision": 7, "content_hash": "sha256:6964e0ef260b795840dbf931ff235a754f74e440bb6e070c5a8a4967a9382d6e", "created_at": "2026-11-01T15:40:45Z", "updated_at": "2026-11-01T22:00:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Screening key genes and signaling pathways in colorectal cancer by integrated bioinformatics analysis.", "doi": "10.3892/mmr.2019.10336", "pmid": "31173250", "authors": ["Chang Yu", "Fuqiang Chen", "Jianjun Jiang", "Hong Zhang", "Meijuan Zhou"], "journal": "Molecular medicine reports", "year": 2019, "abstract": "The aim of the present study was to identify potential key genes associated with the progression and prognosis of colorectal cancer (CRC). Differentially expressed genes (DEGs) between CRC and normal samples were screened by integrated analysis of gene expression profile datasets, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted to identify the biological role of DEGs. In addition, a protein‑protein interaction network and survival analysis were used to identify the key genes. The profiles of GSE9348, GSE22598 and GSE113513 were downloaded from the GEO database. A total of 405 common DEGs were identified, including 236 down‑ and 169 upregulated. GO analysis revealed that the downregulated DEGs were mainly enriched in 'detoxification of copper ion' [biological process, (BP)], 'oxidoreductase activity, acting on CH‑OH group of donors, NAD or NADP as acceptor' [molecular function, (MF)] and 'brush border' [cellular component, (CC)]. Upregulated DEGs were mainly involved in 'nuclear division' (BP), 'snoRNA binding' (MF) and 'nucleolar part' (CC). KEGG pathway analysis revealed that DEGs were mainly involved in 'mineral absorption', 'nitrogen metabolism', 'cell cycle' and 'caffeine metabolism'. A PPI network was constructed with 268 nodes and 1,027 edges. The top one module was selected, and it was revealed that module‑related genes were mainly enriched in the GO terms 'sister chromatid segregation' (BP), 'chemokine activity' (MF), and 'condensed chromosome (CC)'. The KEGG pathway was mainly enriched in 'cell cycle', 'progesterone‑mediated oocyte maturation', 'chemokine signaling pathway', 'IL‑17 signaling pathway', 'legionellosis', and 'rheumatoid arthritis'. DNA topoisomerase II‑α (TOP2A), mitotic arrest deficient 2 like 1 (MAD2L1), cyclin B1 (CCNB1), checkpoint kinase 1 (CHEK1), cell division cycle 6 (CDC6) and ubiquitin conjugating enzyme E2 C (UBE2C) were indicated as hub genes. Furthermore, survival analysis revealed that TOP2A, MAD2L1, CDC6 and CHEK1 may serve as prognostic biomarkers in CRC. The present study provided insights into the molecular mechanism of CRC that may be useful in further investigations.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier analysis was performed based on the expression and clinical data of TCGA, and Perl was used to merge data.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31173250", "locator": "sections[8] \"Survival analysis of hub genes\" paragraph 2", "quote": "Kaplan-Meier analysis was performed based on the expression and clinical data of TCGA, and Perl was used to merge data."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during the present study are included in this article, and the R codes are available at https://github.com/Yuchang66/CRC-project.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31173250", "locator": "sections[19] \"Availability of data and materials\" paragraph 2", "quote": "All data generated or analyzed during the present study are included in this article, and the R codes are available at https://github.com/Yuchang66/CRC-project."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:31173250"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31173250", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3892/mmr.2019.10336", "sha256": 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"PMC6625394", "section_index": 4, "section_title": "Gene expression profile data", "row_count": 5, "column_count": 4}, "table": {"label": "Table I.", "caption": "Information on the datasets included in the current study.", "rows": [["Dataset", "Reference", "Platform", "No. of samples (normal/tumor)"], ["GSE9348", "Hong et al, 2010 (8)", "[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array", "12/12"], ["GSE22598", "Okazaki et al, 2011 (9)", "[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array", "17/17"], ["GSE113513", "Peng et al, 2018 (unpublished)", "[PrimeView] Affymetrix Human Gene Expression Array", "14/14"], ["TCGA_CRC", "The Cancer Genome Atlas (TCGA) data portal", "IlluminaHiseq (Illumina, San Diego, CA)", "51/647"]], "row_count": 5, "column_count": 4, "numeric_cells": 12, "header_rows": 1, "locator": "section[4]/table-wrap[1]#tI-mmr-20-02-1259"}}, {"id": "asset:table:pmid:31173250:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f92d2fcec5abbfd9854a7b847a31ef45933c71ba03fc8bcfe8b243103a5f15ae", "bytes": 2350, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#tII-mmr-20-02-1259", "version": null, "note": "Top 20 down- and upregulated overlapping DEGs in GSE113513, GSE9348, GSE22598 and TCGA were screened by intersected analysis.", "structure": {"pmcid": "PMC6625394", "section_index": 11, "section_title": "Identification of DEGs in GEO and TCGA", "row_count": 41, "column_count": 6}, "table": {"label": "Table II.", "caption": "Top 20 down- and upregulated overlapping DEGs in GSE113513, GSE9348, GSE22598 and TCGA were screened by intersected analysis.", "rows": [["Genes", "GSE113513", "GSE9348", "GSE22598", "TCGA", "Regulation"], ["AQP8", "−4.00", "−6.74", "−2.75", "−6.87", "Down"], ["CLCA4", "−2.30", "−7.61", "−4.91", "−5.35", "Down"], ["GUCA2B", "−4.82", "−5.08", "−3.37", "−6.06", "Down"], ["MS4A12", "−3.68", "−6.04", "−3.54", "−5.36", "Down"], ["GUCA2A", "−4.10", "−5.00", "−3.72", "−5.11", "Down"], ["CA2", "−3.68", "−5.32", "−3.76", "−4.81", "Down"], ["ABCG2", "−2.39", "−6.03", "−3.93", "−4.68", "Down"], ["CLDN8", "−3.69", "−4.40", "−3.65", "−5.07", "Down"], ["GCG", "−4.57", "−3.92", "−4.15", "−4.13", "Down"], ["ZG16", "−3.18", "−4.70", "−4.45", "−4.44", "Down"], ["PKIB", "−3.21", "−4.99", "−3.85", "−3.95", "Down"], ["CA4", "−3.39", "−4.54", "−3.07", "−4.76", "Down"], ["BEST4", "−3.50", "−2.72", "−3.66", "−5.85", "Down"], ["CA1", "−3.33", "−3.20", "−1.94", "−6.51", "Down"], ["MT1M", "−3.29", "−3.90", "−3.35", "−4.30", "Down"], ["CD177", "−2.84", "−4.29", "−2.35", "−5.22", "Down"], ["HSD17B2", "−2.63", "−5.14", "−3.04", "−3.39", "Down"], ["INSL5", "−3.31", "−2.03", "−3.00", "−5.82", "Down"], ["ADH1C", "−3.26", "−3.50", "−3.10", "−4.01", "Down"], ["CLCA1", "−3.45", "−3.77", "−3.62", "−2.54", "Down"], ["FOXQ1", "4.47", "5.16", "5.55", "6.47", "Up"], ["KRT23", "3.69", "4.25", "4.28", "7.37", "Up"], ["LY6G6D", "3.50", "4.09", "3.63", "5.42", "Up"], ["MMP7", "3.15", "3.11", "2.38", "7.03", "Up"], ["CDH3", "2.77", "2.31", "2.76", "5.77", "Up"], ["MMP3", "2.91", "2.94", "2.77", "4.83", "Up"], ["CST1", "1.25", "2.42", "1.00", "8.33", "Up"], ["CRNDE", "3.17", "2.36", "2.73", "4.60", "Up"], ["DPEP1", "2.97", "3.06", "4.14", "2.61", "Up"], ["MMP1", "2.46", "2.59", "3.14", "4.56", "Up"], ["EPHX4", "3.01", "2.32", "2.95", "4.43", "Up"], ["CTHRC1", "1.21", "4.47", "3.15", "3.78", "Up"], ["CLDN1", "2.18", "2.81", "2.74", "4.84", "Up"], ["CEL", "1.56", "2.53", "2.37", "6.10", "Up"], ["CLDN2", "1.54", "2.57", "2.75", "5.57", "Up"], ["SLC35D3", "1.79", "2.97", "3.24", "4.35", "Up"], ["COL11A1", "1.59", "2.49", "1.93", "6.33", "Up"], ["CXCL3", "3.22", "3.60", "2.34", "2.92", "Up"], ["SLCO1B3", "1.43", "1.64", "2.55", "6.44", "Up"], ["CKMT2", "3.33", "2.55", "2.68", "3.46", "Up"]], "row_count": 41, "column_count": 6, "numeric_cells": 170, "header_rows": 1, "locator": "section[11]/table-wrap[1]#tII-mmr-20-02-1259"}}, {"id": "asset:table:pmid:31173250:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:abb9655c6126fc9d411112c656352136c5436d4e2b1877af7a332f0dad8a4eaf", "bytes": 4114, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#tIII-mmr-20-02-1259", "version": null, "note": "GO analysis of down- and upregulated overlapping DEGs associated with CRC.", "structure": {"pmcid": "PMC6625394", "section_index": 12, "section_title": "GO and KEGG enrichment analysis", "row_count": 31, "column_count": 6}, "table": {"label": "Table III.", "caption": "GO analysis of down- and upregulated overlapping DEGs associated with CRC.", "rows": [["Expression", "Terms", "ID", "Description", "q-value", "Genes"], ["Upregulated", "BP", "GO:0000280", "Nuclear division", "4.33×10−7", "RRS1/CKS2/TRIP13/CCND1/FIGNL1/TPX2/ANLN/UBE2C/CHEK1/NUF2/RAD54B/DLGAP5/CDC6/MAD2L1/TOP2A/TTK/CCNB1/ASPM/BUB1B/AURKA"], ["", "BP", "GO:0048285", "Organelle fission", "1.16×10−6", "RRS1/CKS2/TRIP13/CCND1/FIGNL1/TPX2/ANLN/UBE2C/CHEK1/NUF2/RAD54B/DLGAP5/CDC6/MAD2L1/TOP2A/TTK/CCNB1/ASPM/BUB1B/AURKA"], ["", "BP", "GO:0140014", "Mitotic nuclear division", "6.51×10−6", "RRS1/TRIP13/CCND1/TPX2/ANLN/UBE2C/CHEK1/NUF2/DLGAP5/CDC6/MAD2L1/TTK/CCNB1/BUB1B/AURKA"], ["", "BP", "GO:0007088", "Regulation of mitotic nuclear division", "1.18×10−5", "TRIP13/CCND1/ANLN/UBE2C/CHEK1/DLGAP5/CDC6/MAD2L1/TTK/CCNB1/BUB1B/AURKA"], ["", "BP", "GO:0000075", "Cell cycle checkpoint", "1.18×10−5", "TRIP13/CCND1/ARID3A/CHEK1/CDC6/MAD2L1/TOP2A/TTK/CCNB1/SOX4/BUB1B/AURKA/PROX1"], ["", "CC", "GO:0044452", "Nucleolar part", "4.66×10−5", "TAF1D/DKC1/UTP4/WDR43/NOP58/RRS1/RPP40/NUFIP1/ORC6/POLR1D/E2F5"], ["", "CC", "GO:0000793", "Condensed chromosome", "4.66×10−5", "RRS1/SKA3/CHEK1/NUF2/CENPA/MAD2L1/TOP2A/CCNB1/SPC25/ERCC6L/BUB1B/AURKA"], ["", "CC", "GO:0000779", "Condensed chromosome, centromeric region", "5.94×10−5", "SKA3/NUF2/CENPA/MAD2L1/CCNB1/SPC25/ERCC6L/BUB1B/AURKA"], ["", "CC", "GO:0000780", "Condensed nuclear Chromosome, centromeric region", "1.13×10−4", "NUF2/CENPA/CCNB1/BUB1B/AURKA"], ["", "CC", "GO:0000776", "Kinetochore", "1.13×10−4", "SKA3/NUF2/CENPA/MAD2L1/TTK/CCNB1/SPC25/ERCC6L/BUB1B"], ["", "MF", "GO:0030515", "snoRNA binding", "2.99×10−3", "DKC1/NOP58/DDX21/NUFIP1"], ["", "MF", "GO:0009982", "Pseudouridine synthase activity", "3.70×10−3", "PUS1/PUS7/DKC1"], ["", "MF", "GO:0035173", "Histone kinase activity", "7.05×10−3", "CHEK1/CCNB1/AURKA"], ["", "MF", "GO:0001664", "G protein-coupled receptor binding", "8.09×10−3", "CXCL3/RNF43/HOMER1/NMU/CXCL8/ZNRF3/CXCL1/CTHRC1/CXCL5"], ["", "MF", "GO:0140098", "Catalytic activity, acting on RNA", "1.15×10−2", "NOB1/PUS1/EXOSC5/NOP2/RPP40/DDX21/RNASEH2A/POLR1D/RAD54B/AZGP1"], ["Downregulated", "BP", "GO:0010273", "Detoxification of copper ion", "1.22×10−5", "MT1M/MT1X/MT1E/MT1H/MT1F/MT1G"], ["", "BP", "GO:1990169", "Stress response to copper ion", "1.22×10−5", "MT1M/MT1X/MT1E/MT1H/MT1F/MT1G"], ["", "BP", "GO:0061687", "Detoxification of inorganic compound", "1.22×10−5", "MT1M/MT1X/MT1E/MT1H/MT1F/MT1G"], ["", "BP", "GO:0071280", "Cellular response to copper ion", "1.22×10−5", "MT1M/MT1X/MT1E/MT1H/MT1F/MT1G/AOC1"], ["", "BP", "GO:0097501", "Stress response to metal ion", "1.35×10−5", "MT1M/MT1X/MT1E/MT1H/MT1F/MT1G"], ["", "CC", "GO:0005903", "Brush border", "6.96×10−5", "CDHR5/TRPM6/SCIN/CDHR2/CA4/LIMA1/CYBRD1/MYO1A/SLC26A3/SI"], ["", "CC", "GO:0045177", "Apical part of cell", "3.15×10−4", "ABCG2/CA2/RAB27A/CDHR5/PTPRH/TRPM6/AQP8/CDHR2/CA4/SCNN1B/CLCA4/CEACAM1/FABP1/CEACAM7/MYO1A/SLC26A3/SI"], ["", "CC", "GO:0031526", "Brush border membrane", "3.15×10−4", "CDHR5/TRPM6/CDHR2/CA4/LIMA1/CYBRD1/SLC26A3"], ["", "CC", "GO:0005902", "Microvillus", "6.78×10−4", "CA2/CDHR5/PTPRH/CDHR2/CEACAM1/CLCA1/AOC3/MYO1A"], ["", "CC", "GO:0098862", "Cluster of actin-based cell projections", "8.31×10−4", "CDHR5/TRPM6/SCIN/CDHR2/CA4/LIMA1/CYBRD1/MYO1A/SLC26A3/SI"], ["", "MF", "GO:0016616", "Oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor", "6.48×10−5", "UGDH/ADH1B/HPGD/LDHD/ADH1C/DHRS11/DHRS9/HSD17B2/AKR1B10/HSD11B2/BMP2"], ["", "MF", "GO:0016614", "Oxidoreductase activity, acting on CH-OH group of donors", "1.09×10−4", "UGDH/ADH1B/HPGD/LDHD/ADH1C/DHRS11/DHRS9/HSD17B2/AKR1B10/HSD11B2/BMP2"], ["", "MF", "GO:0004089", "Carbonate dehydratase activity", "1.26×10−4", "CA7/CA2/CA12/CA1/CA4"], ["", "MF", "GO:0048038", "Quinone binding", "4.90×10−3", "ETFDH/TP53I3/AOC3/AOC1"], ["", "MF", "GO:0033764", "Steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor", "1.52×10−2", "DHRS11/DHRS9/HSD17B2/HSD11B2"]], "row_count": 31, "column_count": 6, "numeric_cells": 81, "header_rows": 1, "locator": "section[12]/table-wrap[1]#tIII-mmr-20-02-1259"}}, {"id": "asset:table:pmid:31173250:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:aad2bbd6518e1938069d4f053360e8ebae7e5cf2cc2b17cda81a78db54e1c691", "bytes": 1961, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#tIV-mmr-20-02-1259", "version": null, "note": "GO analysis of selected module-associated DEGs.", "structure": {"pmcid": "PMC6625394", "section_index": 13, "section_title": "PPI network and module selection", "row_count": 15, "column_count": 5}, "table": {"label": "Table IV.", "caption": "GO analysis of selected module-associated DEGs.", "rows": [["ID", "GO Terms", "Ontology", "q-value", "Genes"], ["GO:0000819", "Sister chromatid segregation", "BP", "5.54×10−13", "BUB1B/CCNB1/CDC6/CENPA/DLGAP5/ERCC6L/MAD2L1/NUF2/SPC25/TOP2A/TRIP13/TTK/UBE2C"], ["GO:0007088", "Regulation of mitotic nuclear division", "BP", "8.77×10−12", "ANLN/AURKA/BUB1B/CCNB1/CDC6/CHEK1/DLGAP5/MAD2L1/TRIP13/TTK/UBE2C"], ["GO:0098813", "Nuclear chromosome", "BP", "1.24×10−11 segregation", "BUB1B/CCNB1/CDC6/CENPA/DLGAP5/ERCC6L/MAD2L1/NUF2/SPC25/TOP2A/TRIP13/TTK/UBE2C"], ["GO:0051304", "Chromosome separation", "BP", "1.37×10−11", "BUB1B/CCNB1/CDC6/DLGAP5/MAD2L1/TOP2A/TRIP13/TTK/UBE2C"], ["GO:0030071", "Regulation of mitotic metaphase/anaphase transition", "BP", "1.46×10−11", "BUB1B/CCNB1/CDC6/DLGAP5/MAD2L1/TRIP13/TTK/UBE2C"], ["GO:0000793", "Condensed chromosome", "CC", "2.53×10−10", "AURKA/BUB1B/CCNB1/CENPA/CHEK1/ERCC6L/MAD2L1/NUF2/SKA3/SPC25/TOP2A"], ["GO:0000779", "Condensed chromosome/centromeric region", "CC", "5.40×10−10", "AURKA/BUB1B/CCNB1/CENPA/ERCC6L/MAD2L1/NUF2/SKA3/SPC25"], ["GO:0000775", "Chromosome/centromeric region", "CC", "1.59×10−9", "AURKA/BUB1B/CCNB1/CENPA/ERCC6L/MAD2L1/NUF2/SKA3/SPC25/TTK"], ["GO:0000776", "Kinetochore", "CC", "1.80×10−9", "BUB1B/CCNB1/CENPA/ERCC6L/MAD2L1/NUF2/SKA3/SPC25/TTK"], ["GO:0000777", "Condensed chromosome kinetochore", "CC", "8.17×10−9", "BUB1B/CCNB1/CENPA/ERCC6L/MAD2L1/NUF2/SKA3/SPC25"], ["GO:0008009", "Chemokine activity", "MF", "1.41×10−9", "CCL19/CCL28/CXCL1/CXCL12/CXCL3/CXCL5/CXCL8"], ["GO:0042379", "Chemokine receptor binding", "MF", "8.09×10−9", "CCL19/CCL28/CXCL1/CXCL12/CXCL3/CXCL5/CXCL8"], ["GO:0045236", "CXCR chemokine receptor binding", "MF", "1.46×10−8", "CXCL1/CXCL12/CXCL3/CXCL5/CXCL8"], ["GO:0035173", "Histone kinase activity", "MF", "1.99×10−4", "AURKA/CCNB1/CHEK1"]], "row_count": 15, "column_count": 5, "numeric_cells": 41, "header_rows": 1, "locator": "section[13]/table-wrap[1]#tIV-mmr-20-02-1259"}}, {"id": "asset:table:pmid:31173250:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:89b33939fc06e24d639ffa14a5c7aa91ac45a40ea10149ff01807f900ec78908", "bytes": 724, "access": "open", "state": "verified", 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