Screening Hub Genes as Prognostic Biomarkers of Hepatocellular Carcinoma by Bioinformatics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31822116", "kind": "science-record", "revision": 8, "content_hash": "sha256:f31229363cfc5cdc2cf567298623de48d743c16f4bb25639e711a8a652cb89dd", "created_at": "2026-11-01T15:40:53Z", "updated_at": "2026-11-01T22:01:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Screening Hub Genes as Prognostic Biomarkers of Hepatocellular Carcinoma by Bioinformatics Analysis.", "doi": "10.1177/0963689719893950", "pmid": "31822116", "authors": ["Zengyuan Zhou", "Yuzheng Li", "Haiyue Hao", "Yuanyuan Wang", "Zihao Zhou", "Zhipeng Wang", "Xia Chu"], "journal": "Cell transplantation", "year": 2019, "abstract": "Hepatocellular carcinoma (HCC) is a widespread, common type of cancer in Asian countries, and the need for biomarker-matched molecularly targeted therapy for HCC has been increasingly recognized. However, the effective treatment for HCC is unclear. Therefore, identifying additional hub genes and pathways as novel prognostic biomarkers for HCC is necessary. In this study, the expression profiles of GSE121248, GSE45267 and GSE84402 were obtained from the Gene Expression Omnibus (GEO), including 132 HCC and 90 noncancerous liver tissues. Differentially expressed genes (DEGs) between HCC and noncancerous samples were identified by GEO2 R and Venn diagrams. In total, 109 DEGs were identified in these datasets, including 24 upregulated genes and 85 downregulated genes. Subsequently, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) preliminary analyses of the DEGs were performed using DAVID. The protein-protein interaction (PPI) network of the DEGs was constructed with the Search Tool for the Retrieval of Interacting Genes (STRING) and visualized in Cytoscape. Module analysis of the PPI network was performed using MCODE to get hub genes. Moreover, the influence of the hub genes on overall survival was determined with Kaplan-Meier plotter. All hub genes were analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) and KEGG. Overall, the hub genes DTL, CDK1, CCNB1, RACGAP1, ECT2, NEK2, BUB1B, PBK, TOP2A, ASPM, HMMR, RRM2, CDKN3, PRC1, and ANLN were upregulated in HCC, and the survival rate was lower for HCC with increased expression of these hub genes. CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway, and CCNB1, CDK1, and BUB1B were enriched in the cell cycle. In brief, we screened 15 hub genes and pathways to identify potential prognostic markers for HCC treatment. However, the specific occurrence and development of HCC with expression of the hub genes should be verified in vivo and in vitro.", "claims": [{"id": "claim-data-access", "statement": "Three microarray datasets from the GPL570 platform ([HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array) were downloaded from the GEO (http://www.ncbi.nlm.nih.gov/geo/). The GSE121248 expression profile contains 70 HCC samples and 37 noncancerous samples derived from the National Cancer Centre Singapore10.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31822116", "locator": "sections[3] \"Datasets from the GEO\" paragraph 2", "quote": "Three microarray datasets from the GPL570 platform ([HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array) were downloaded from the GEO (http://www.ncbi.nlm.nih.gov/geo/). The GSE121248 expression profile contains 70 HCC samples and 37 noncancerous samples derived from the National Cancer Centre Singapore10."}], "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:31822116"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE121248"], "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": ["data:geo:GSE121248"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31822116", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1177/0963689719893950", "sha256": "sha256:209b1682f7a397e5ebde358fe49617ec06b9ecece0336addbacdf24b8cb10ba1", "bytes": 35129, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1177/0963689719893950", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7016461", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE121248", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121248", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE121248", "version": null, "note": "Three microarray datasets from the GPL570 platform ([HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array) were downloaded from the GEO (http://www.ncbi.nlm.nih.gov/geo/). 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false}}, {"id": "asset:table:pmid:31822116:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0fb534a3bf3dddc16a51755fcb7ce759078557eef75438c90cdf2d5bbeac5fb7", "bytes": 1147, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#table1-0963689719893950", "version": null, "note": "Identification of the Up- and Downregulated DEGs in HCC Tissues Compared with Noncancerous Liver Tissues.", "structure": {"pmcid": "PMC7016461", "section_index": 9, "section_title": "Identification of the DEGs between HCC and Noncancerous Tissues", "row_count": 3, "column_count": 2}, "table": {"label": "Table 1.", "caption": "Identification of the Up- and Downregulated DEGs in HCC Tissues Compared with Noncancerous Liver Tissues.", "rows": [["DEGs", "Gene names"], ["Upregulated", "CDK1, CAP2, DTL, PEG10, RACGAP1, CTHRC1, IGF2BP3, RRM2, CCNB1, TOP2A, ASPM, HMMR, CDKN3, PBK, GPC3, SULT1C2, NEK2, ANLN, ACSL4, DUXAP10, CRNDE, BUB1B, ECT2, PRC1"], ["Downregulated", "CYP4A22///CYP4A11, CYP26A1, BBOX1, CYP2A6, SERPINE1, PGLYRP2, LINC01093, CXCL14, SLC22A1, IGF1, CYP39A1, HAO2, IGHM, FAM134B, MT1F, SLC25A47, MFSD2A, ZG16, FLJ22763, HHIP, KCNN2, SLCO1B3, CYP1A2, CNDP1, BCO2, ACSM3, FCN3, GBA3, PDGFRA, TTC36, CLEC4G, C3P1, CDH19, CYP2B6, GYS2, FOLH1B, KMO, CD5 L, LPA, GHR, CLEC1B, CXCL2, FOSB, LIFR, FAM65C, CYP2C9, CLRN3, CYP2A7, LCAT, CLEC4 M, ESR1, FOS, LOC101928916///NNMT, PLAC8, ALDOB, HAMP, DNASE1L3, DCN, NAT2, BCHE, AKR1D1, TMEM27, CRHBP, THRSP, IDO2, HGFAC, IGHA2///IGHA1///IGH, C7, ADH4, GPM6A, OIT3, MT1 M, HGF, GLYAT, CYP2B7P///CYP2B6, JCHAIN, GLS2, SRD5A2, ADRA1A, EGR1, APOF, C9, SRPX, FCN2, LINC00844"]], "row_count": 3, "column_count": 2, "numeric_cells": 2, "header_rows": 1, "locator": "section[9]/table-wrap[1]#table1-0963689719893950"}}, {"id": "asset:table:pmid:31822116:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ae59bb9560119005bce374707d5cccc0d1903e55aa0646c7d5359177fae064bd", "bytes": 3496, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#table2-0963689719893950", "version": null, "note": "GO Enrichment Analysis of the Up- and Downregulated DEGs.", "structure": {"pmcid": "PMC7016461", "section_index": 10, "section_title": "GO and KEGG Enrichment Analysis of the DEGs", "row_count": 31, "column_count": 7}, "table": {"label": "Table 2.", "caption": "GO Enrichment Analysis of the Up- and Downregulated DEGs.", "rows": [["Expression", "Category", "Term", "Count", "%", "p-value", "FDR"], ["Upregulated", "GOTERM_BP_DIRECT", "GO:0007067∼mitotic nuclear division", "6", "25", "1.13E-05", "0.0147121"], ["GOTERM_BP_DIRECT", "GO:0051988∼regulation of attachment of spindle microtubules to kinetochore", "3", "12.5", "3.12E-05", "0.040502664"], ["", "GOTERM_BP_DIRECT", "GO:0000086∼G2/M transition of mitotic cell cycle", "4", "16.67", "6.34E-04", "0.821644638"], ["", "GOTERM_CC_DIRECT", "GO:0030496∼midbody", "6", "25", "3.05E-07", "3.20E-04"], ["", "GOTERM_CC_DIRECT", "GO:0005737∼cytoplasm", "17", "70.83", "8.67E-06", "0.009070333"], ["", "GOTERM_CC_DIRECT", "GO:0072686∼mitotic spindle", "3", "12.5", "0.001009", "1.05139872"], ["", "GOTERM_CC_DIRECT", "GO:0005829∼cytosol", "11", "45.83", "0.001941", "2.012816159"], ["", "GOTERM_CC_DIRECT", "GO:0005634∼nucleus", "14", "58.33", "0.002201", "2.280305423"], ["", "GOTERM_MF_DIRECT", "GO:0035173∼histone kinase activity", "2", "8.33", "0.004967", "5.022871579"], ["", "GOTERM_MF_DIRECT", "GO:0005515∼protein binding", "18", "75", "0.006112", "6.147950372"], ["", "GOTERM_MF_DIRECT", "GO:0004672∼protein kinase activity", "4", "16.67", "0.009546", "9.450412521"], ["", "GOTERM_MF_DIRECT", "GO:0004674∼protein serine/threonine kinase activity", "4", "16.67", "0.010824", "10.6521653"], ["", "GOTERM_MF_DIRECT", "GO:0005524∼ATP binding", "6", "25", "0.033186", "29.48034821"], ["Downregulated", "GOTERM_BP_DIRECT", "GO:0019373∼epoxygenase P450 pathway", "5", "6.17", "1.01E-06", "0.001505249"], ["GOTERM_BP_DIRECT", "GO:0055114∼oxidation-reduction process", "14", "17.28", "1.65E-06", "0.0024543"], ["", "GOTERM_BP_DIRECT", "GO:0042738∼exogenous drug catabolic process", "4", "4.94", "1.76E-05", "0.026056805"], ["", "GOTERM_BP_DIRECT", "GO:0006805∼xenobiotic metabolic process", "6", "7.41", "2.38E-05", "0.035330156"], ["", "GOTERM_BP_DIRECT", "GO:0032787∼monocarboxylic acid metabolic process", "3", "3.70", "5.73E-05", "0.084993128"], ["", "GOTERM_BP_DIRECT", "GO:0017144∼drug metabolic process", "4", "4.94", "2.23E-04", "0.329889509"], ["", "GOTERM_CC_DIRECT", "GO:0031090∼organelle membrane", "8", "9.88", "6.75E-08", "7.45E-05"], ["", "GOTERM_CC_DIRECT", "GO:0005576∼extracellular region", "23", "28.40", "2.98E-07", "3.29E-04"], ["", "GOTERM_CC_DIRECT", "GO:0072562∼blood microparticle", "7", "8.64", "3.82E-05", "0.042171314"], ["", "GOTERM_CC_DIRECT", "GO:0005615∼extracellular space", "15", "18.52", "0.001068", "1.172144989"], ["", "GOTERM_MF_DIRECT", "GO:0020037∼heme binding", "8", "9.88", "1.72E-06", "0.002191179"], ["", "GOTERM_MF_DIRECT", "GO:0005506∼iron ion binding", "8", "9.88", "3.58E-06", "0.004576749"], ["", "GOTERM_MF_DIRECT", "GO:0016705∼oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen", "6", "7.41", "4.03E-06", "0.005148689"], ["", "GOTERM_MF_DIRECT", "GO:0016712∼oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen", "4", "4.94", "3.13E-05", "0.039961043"], ["", "GOTERM_MF_DIRECT", "GO:0008392∼arachidonic acid epoxygenase activity", "4", "4.94", "3.13E-05", "0.039961043"], ["", "GOTERM_MF_DIRECT", "GO:0019825∼oxygen binding", "5", "6.17", "4.47E-05", 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