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pmid:32476992
Bioinformatics Analysis based on Multiple Databases Identifies Hub Genes Associated with Hepatocellular Carcinoma.
Lu Zeng · Xiude Fan · Xiaoyun Wang · Huan Deng · Kun Zhang · Xiaoge Zhang · Shan He · Na Li · Qunying Han · Zhengwen Liu
Current genomics · 2019 doi:10.2174/1389202920666191011092410
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32476992", "kind": "science-record", "revision": 5, "content_hash": "sha256:89d1e3c7bbef62189f8ebdb90522f9c2dad33670bc434bf31db3f08e66fc3688", "created_at": "2026-11-01T15:41:02Z", "updated_at": "2026-11-01T22:01:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics Analysis based on Multiple Databases Identifies Hub Genes Associated with Hepatocellular Carcinoma.", "doi": "10.2174/1389202920666191011092410", "pmid": "32476992", "authors": ["Lu Zeng", "Xiude Fan", "Xiaoyun Wang", "Huan Deng", "Kun Zhang", "Xiaoge Zhang", "Shan He", "Na Li", "Qunying Han", "Zhengwen Liu"], "journal": "Current genomics", "year": 2019, "abstract": "BACKGROUND: Hepatocellular carcinoma (HCC) is the most common liver cancer and the mechanisms of hepatocarcinogenesis remain elusive.\nOBJECTIVE: This study aims to mine hub genes associated with HCC using multiple databases.\nMETHODS: Data sets GSE45267, GSE60502, GSE74656 were downloaded from GEO database. Differentially expressed genes (DEGs) between HCC and control in each set were identified by limma software. The GO term and KEGG pathway enrichment of the DEGs aggregated in the datasets (aggregated DEGs) were analyzed using DAVID and KOBAS 3.0 databases. Protein-protein interaction (PPI) network of the aggregated DEGs was constructed using STRING database. GSEA software was used to verify the biological process. Association between hub genes and HCC prognosis was analyzed using patients' information from TCGA database by survminer R package.\nRESULTS: From GSE45267, GSE60502 and GSE74656, 7583, 2349, and 553 DEGs were identified respectively. A total of 221 aggregated DEGs, which were mainly enriched in 109 GO terms and 29 KEGG pathways, were identified. Cell cycle phase, mitotic cell cycle, cell division, nuclear division and mitosis were the most significant GO terms. Metabolic pathways, cell cycle, chemical carcinogenesis, retinol metabolism and fatty acid degradation were the main KEGG pathways. Nine hub genes (TOP2A, NDC80, CDK1, CCNB1, KIF11, BUB1, CCNB2, CCNA2 and TTK) were selected by PPI network and all of them were associated with prognosis of HCC patients.\nCONCLUSION: TOP2A, NDC80, CDK1, CCNB1, KIF11, BUB1, CCNB2, CCNA2 and TTK were hub genes in HCC, which may be potential biomarkers of HCC and targets of HCC therapy.", "claims": [{"id": "claim-method", "statement": "The association between each hub gene and prognosis of HCC patients was analyzed using “survminer” package [18] and p < 0.05 (unadjusted p value) was considered significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32476992", "locator": "sections[7] \"Overall Survival Analysis\" paragraph 2", "quote": "The association between each hub gene and prognosis of HCC patients was analyzed using “survminer” package [18] and p < 0.05 (unadjusted p value) was considered significant."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors confirm that the data supporting the results and findings of this study are available within the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32476992", "locator": "sections[21] \"AVAILABILITY OF DATA AND MATERIALS\" paragraph 2", "quote": "The authors confirm that the data supporting the results and findings of this study are available within the article."}], "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:32476992"], "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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"structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The authors confirm that the data supporting the results and findings of this study are available within the article.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1100370", "GSM1100371", "GSM1100372", "GSM1100373", "GSM1100374", "GSM1100375", "GSM1100376", "GSM1100377", "GSM1100378", "GSM1100379", "GSM1100380", "GSM1100381", "GSM1100382", "GSM1100383", "GSM1100384", "GSM1100385", "GSM1100386", "GSM1100387", "GSM1100388", "GSM1100389", "GSM1100390", "GSM1100391", "GSM1100392", "GSM1100393", "GSM1100394", "GSM1100395", "GSM1100396", "GSM1100397", "GSM1100398", "GSM1100399", "GSM1100400", "GSM1100401", "GSM1100402", "GSM1100403", "GSM1100404", "GSM1100405", "GSM1100406", "GSM1100407", "GSM1100408", "GSM1100409", "GSM1100410", "GSM1100411", "GSM1100412", "GSM1100413", "GSM1100414", "GSM1100415", "GSM1100416", "GSM1100417", "GSM1100418", "GSM1100419", 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"asset:table:pmid:32476992:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0649ed7194e4db100e5006b80a4fe7d7ffe6be715f45752bf3ade26146bd09fb", "bytes": 1106, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#T1", "version": null, "note": "The top 20 up-regulated and down-regulated DEGs aggregated in GSE45267, GSE60502 and GSE74656.", "structure": {"pmcid": "PMC7235396", "section_index": 9, "section_title": "Screening of DEGs Aggregated in the Datasets", "row_count": 21, "column_count": 4}, "table": {"label": "Table 1", "caption": "The top 20 up-regulated and down-regulated DEGs aggregated in GSE45267, GSE60502 and GSE74656.", "rows": [["Up-regulated Genes", "Score", "Down-regulated Genes", "Score"], ["NDC80", "3.81E-08", "FCN3", "1.16E-08"], ["SPINK1", "4.89E-07", "HAMP", "1.47E-07"], ["RACGAP1", "7.81E-06", "APOF", "2.20E-07"], ["ACSL4", "7.81E-06", "CYP1A2", "2.64E-07"], ["GINS1", "1.09E-05", "SLC22A1", "4.30E-07"], ["PLVAP", "2.10E-05", "CRHBP", "9.44E-07"], ["EZH2", "4.16E-05", "GYS2", "9.44E-07"], ["GPC3", "5.91E-05", "HGFAC", "5.23E-06"], ["CEP55", "6.25E-05", "AKR1D1", "6.32E-06"], ["DLGAP5", "7.43E-05", "CLEC4M", "6.32E-06"], ["CENPE", "8.95E-05", "MT1F", "1.05E-05"], ["CDC20", "0.00011", "CFHR4", "1.77E-05"], ["TOP2A", "0.000125", "LPA", "2.09E-05"], ["TTK", "0.000141", "DNASE1L3", "2.65E-05"], ["KNTC1", "0.000187", "MT1E", "2.75E-05"], ["ZWILCH", "0.000194", "GNMT", "3.54E-05"], ["NUSAP1", "0.000258", "KCNN2", "3.66E-05"], ["CTHRC1", "0.000258", "CFP", "3.79E-05"], ["SHCBP1", "0.000278", "CYP2B6", "4.32E-05"], ["NCAPG", "0.000281", "CYP2E1", "4.98E-05"]], "row_count": 21, "column_count": 4, "numeric_cells": 44, "header_rows": 1, "locator": "section[9]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:32476992:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:81c3966d22de1d194f66bf534fabfefce4f0ddf63ca0e79b1c87e463a1ca2f72", "bytes": 3073, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#T2", "version": null, "note": "The main GO terms of the DEGs aggregated in GSE45267, GSE60502 and GSE74656.", "structure": {"pmcid": "PMC7235396", "section_index": 10, "section_title": "GO Analysis", "row_count": 16, "column_count": 6}, "table": {"label": "Table 2", "caption": "The main GO terms of the DEGs aggregated in GSE45267, GSE60502 and GSE74656.", "rows": [["Category", "ID", "Term", "Count", "adj_pval", "Genes"], ["BP", "GO:0022403", "cell cycle phase", "31", "5.57E-14", "PRC1, NEK2, DBF4, KNTC1, TTK, CEP55, KIF2C, SAC3D1, NCAPG, BUB1, ZWILCH, CCNA2, ASPM, CDCA3, CDC7, CDK1, KIF11, DLGAP5,TPX2, NUSAP1, CENPE, NDC80, CDC20, PBK, TACC3, CDK4, CDKN3, CCNB1, CCNB2, CKS2, BUB1B"], ["BP", "GO:0000278", "mitotic cell cycle", "29", "1.45E-13", "PRC1, NEK2, DBF4, KNTC1, TTK, CEP55, KIF2C, SAC3D1, NCAPG, BUB1, ZWILCH, CCNA2, ASPM, CDCA3, CDC7, CDK1, KIF11, DLGAP5,TPX2, NUSAP1, CENPE, NDC80, CDC20, PBK, CDK4, CDKN3, CCNB1, CCNB2, BUB1B"], ["BP", "GO:0051301", "cell division", "26", "2.62E-13", "PRC1, NEK2, KNTC1, CEP55, SAC3D1, NCAPG, BUB1, ZWILCH, CCNA2, ASPM, CDCA3, CDC7, CDK1, KIF11, NUSAP1, CENPE, NDC80,CDC20, CDK4, RACGAP1, MCM5, CCNB1, CCNB2, CKS2, BUB1B, CDCA7L"], ["BP", "GO:0000280", "nuclear division", "23", "2.76E-13", "CDK1, KIF11, NEK2, DLGAP5, TPX2, KNTC1, NUSAP1, NDC80, CENPE, CDC20, PBK, CEP55, CCNB1, KIF2C, CCNB2, SAC3D1, NCAPG,BUB1, BUB1B, ZWILCH, CCNA2, ASPM, CDCA3"], ["BP", "GO:0007067", "mitosis", "23", "2.76E-13", "CDK1, KIF11, NEK2, DLGAP5, TPX2, KNTC1, NUSAP1, NDC80, CENPE, CDC20, PBK, CEP55, CCNB1, KIF2C, CCNB2, SAC3D1, NCAPG,BUB1, BUB1B, ZWILCH, CCNA2, ASPM, CDCA3"], ["MF", "GO:0009055", "electron carrier activity", "21", "1.35E-11", "CYP3A4, STEAP3, GCDH, CYP2C19, CYP2B6, ADH6, CYP26A1, KMO, CYP4F12, CYP2E1, CYP1A2, CYP4A11, CYP39A1, HAAO, CYP2A6,AKR7A3, CYP2A7, CYP4F2, RDH16"], ["MF", "GO:0019825", "oxygen binding", "11", "1.78E-10", "CYP3A4, CYP4A11, CYP2C19, CYP2B6, HAAO, CYP26A1, CYP2A7, CYP4F12, CYP2E1, CYP1A2, CYP4F2"], ["MF", "GO:0020037", "heme binding", "13", "7.11E-08", "CYP3A4, CYP4A11, CYP39A1, CYP27A1, CYP2C19, CYP2B6, CYP26A1, CYP2A6, CYP2A7, CYP4F12, CYP2E1, CYP1A2, CYP4F2"], ["MF", "GO:0046870", "cadmium ion binding", "6", "9.47E-08", "MT1M, MT1E, MT1H, MT1G, MT1X, MT1F"], ["MF", "GO:0046906", "tetrapyrrole binding", "13", "1.45E-07", "CYP3A4, CYP4A11, CYP39A1, CYP27A1, CYP2C19, CYP2B6, CYP26A1, CYP2A6, CYP2A7, CYP4F12, CYP2E1, CYP1A2, CYP4F2"], ["CC", "GO:0005819", "spindle", "18", "1.40E-11", "CDK1, KIF4A, KIF11, PRC1, NEK2, DLGAP5, KNTC1, TPX2, NUSAP1, TTK, CENPE, CDC20, CBX1, RACGAP1, SAC3D1, BUB1, BUB1B, ASPM"], ["CC", "GO:0005792", "microsome", "18", "2.37E-08", "CYP3A4, AQP9, CYP2C19, CYP2B6, IGFALS, CYP26A1, CYP4F12, CYP2E1, CYP1A2, CYP4A11, CYP39A1, CYP2A6, SORT1, CYP2A7,SRD5A2, CYP4F2, ACSL4, RDH16"], ["CC", "GO:0042598", "vesicular fraction", "18", "3.64E-08", "CYP3A4, AQP9, CYP2C19, CYP2B6, IGFALS, CYP26A1, CYP4F12, CYP2E1, CYP1A2, CYP4A11, CYP39A1, CYP2A6, SORT1, CYP2A7,SRD5A2, CYP4F2, ACSL4, RDH16"], ["CC", "GO:0000777", "condensed chromosome kinetochore", "10", "7.84E-08", "KIF2C, CENPM, HJURP, KNTC1, BUB1, BUB1B, CENPE, NDC80, CENPK, ZWILCH"], ["CC", "GO:0000779", "condensed chromosome, centromeric region", "10", "2.48E-07", "KIF2C, CENPM, HJURP, KNTC1, BUB1, BUB1B, CENPE, NDC80, CENPK, ZWILCH"]], "row_count": 16, "column_count": 6, "numeric_cells": 59, "header_rows": 1, "locator": "section[10]/table-wrap[1]#T2"}}, {"id": "asset:table:pmid:32476992:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a435b08c2e5c4314e6fc6a5a4c36da05959d48c8d254ff266cc45e1e1c93b982", "bytes": 1985, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#T3", "version": null, "note": "The KEGG pathways of the DEGs aggregated in GSE45267, GSE60502 and GSE74656.", "structure": {"pmcid": "PMC7235396", "section_index": 11, "section_title": "Enriched KEGG Pathways", "row_count": 30, "column_count": 5}, "table": {"label": "Table 3", "caption": "The KEGG pathways of the DEGs aggregated in GSE45267, GSE60502 and GSE74656.", "rows": [["S. No.", "Term", "ID", "Input Number", "p"], ["1", "Metabolic pathways", "hsa01100", "38", "8.71E-12"], ["2", "Cell cycle", "hsa04110", "13", "1.48E-10"], ["3", "Chemical carcinogenesis", "hsa05204", "10", "5.45E-09"], ["4", "Retinol metabolism", "hsa00830", "9", "1.18E-08"], ["5", "Fatty acid degradation", "hsa00071", "8", "1.36E-08"], ["6", "Metabolism of xenobiotics by cytochrome P450", "hsa00980", "9", "2.65E-08"], ["7", "Drug metabolism - cytochrome P450", "hsa00982", "8", "2.46E-07"], ["8", "Tyrosine metabolism", "hsa00350", "6", "1.13E-06"], ["9", "p53 signaling pathway", "hsa04115", "7", "3.51E-06"], ["10", "Mineral absorption", "hsa04978", "6", "9.06E-06"], ["11", "Progesterone-mediated oocyte maturation", "hsa04914", "7", "2.80E-05"], ["12", "Caffeine metabolism", "hsa00232", "3", "3.15E-05"], ["13", "Glycolysis / Gluconeogenesis", "hsa00010", "6", "3.43E-05"], ["14", "Tryptophan metabolism", "hsa00380", "5", "3.66E-05"], ["15", "Oocyte meiosis", "hsa04114", "7", "0.0001"], ["16", "Linoleic acid metabolism", "hsa00591", "4", "0.000182"], ["17", "Steroid hormone biosynthesis", "hsa00140", "5", "0.000216"], ["18", "Arachidonic acid metabolism", "hsa00590", "5", "0.000286"], ["19", "Prion diseases", "hsa05020", "4", "0.000313"], ["20", "Bile secretion", "hsa04976", "5", "0.000448"], ["21", "PPAR signaling pathway", "hsa03320", "5", "0.000505"], ["22", "Primary bile acid biosynthesis", "hsa00120", "3", "0.000594"], ["23", "Complement and coagulation cascades", "hsa04610", "5", "0.00071"], ["24", "Drug metabolism - other enzymes", "hsa00983", "4", "0.000815"], ["25", "Melanoma", "hsa05218", "4", "0.004018"], ["26", "AMPK signaling pathway", "hsa04152", "5", "0.004832"], ["27", "FoxO signaling pathway", "hsa04068", "5", "0.006584"], ["28", "HTLV-I infection", "hsa05166", "7", "0.007323"], ["29", "Valine, leucine and isoleucine degradation", "hsa00280", "3", "0.008979"]], "row_count": 30, "column_count": 5, "numeric_cells": 119, "header_rows": 1, "locator": "section[11]/table-wrap[1]#T3"}}, {"id": "asset:table:pmid:32476992:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b632da9ff8854ea0b138d21203aed590c0b055c645f0eb152c63277efe85dbc1", "bytes": 832, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#T4", "version": null, "note": "The HCC enrichment gene sets in GSE45267 by GSEA database.", "structure": {"pmcid": "PMC7235396", "section_index": 13, "section_title": "GSEA Analysis", "row_count": 6, "column_count": 5}, "table": {"label": "Table 4", "caption": "The HCC enrichment gene sets in GSE45267 by GSEA database.", "rows": [["Enrichment Gene Set", "NES", "NOM p-val", "FDR", "Top Ten Core Enriched Genes"], ["MITOTIC_SPINDLE", "1.611", "0.002", "0.214", "TTK, NDC80, RACGAP1, KIF4A, PRC1,TOP2A, ANLN, DLGAP5, KIF11, NUSAP1"], ["G2M_CHECKPOINT", "1.553", "0.004", "0.125", "TTK, NDC80, CDKN3, RACGAP1, KIF4A,PRC1, TOP2A, PBK, CDC20, HMMR"], ["E2F_TARGETS", "1.540", "0.004", "0.070", "GINS1, CDKN3, RACGAP1, KIF4A, TOP2A,BUB1B, CDC20, HMMR, EZH2, DLGAP5"], ["SPERMATOGENESIS", "1.550", "0.020", "0.097", "TTK, CDKN3, EZH2, NEK2, AURKA,CDK1, RFC4, CLGN, KIF2C, RPL39L"], ["DNA_REPAIR", "1.578", "0.032", "0.151", "ZWINT, RFC4, PRIM1, SAC3D1, FEN1,POLA1, TYMS, RFC5, PCNA, POLR3C"]], "row_count": 6, "column_count": 5, "numeric_cells": 19, "header_rows": 1, "locator": "section[13]/table-wrap[1]#T4"}}], "gaps": ["asset:data:geo:GSE45267 not downloaded", "asset:data:geo:GSE45267 licence not read", "asset:data:geo:GSE60502 not downloaded", "asset:data:geo:GSE60502 licence not read", "asset:data:geo:GSE74656 not downloaded", "asset:data:geo:GSE74656 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.7, "band": "medium", "quote": "limma"}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Protein-protein interaction"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"id": "method-4", "family": null, "specific": null, "label": "survminer R package", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The association between each hub gene and prognosis of HCC patients was analyzed using “survminer” package [18] and p < 0.05 (unadjusted p value) was considered significant."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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