Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33193629", "kind": "science-record", "revision": 7, "content_hash": "sha256:be1ed1d826a67e5afde42fff691ee4015a5afc0777ae702169c052e8a8dfbfc2", "created_at": "2026-11-01T15:41:16Z", "updated_at": "2026-11-01T22:02:31Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis.", "doi": "10.3389/fgene.2020.555537", "pmid": "33193629", "authors": ["Xian-Chang Zeng", "Lu Zhang", "Wen-Jun Liao", "Lu Ao", "Ze-Man Lin", "Wen Kang", "Wan-Nan Chen", "Xu Lin"], "journal": "Frontiers in genetics", "year": 2020, "abstract": "Hepatocellular carcinoma (HCC) is one of the most lethal cancers globally. Hepatitis B virus (HBV) infection might cause chronic hepatitis and cirrhosis, leading to HCC. To screen prognostic genes and therapeutic targets for HCC by bioinformatics analysis and determine the mechanisms underlying HBV-related HCC, three high-throughput RNA-seq based raw datasets, namely GSE25599, GSE77509, and GSE94660, were obtained from the Gene Expression Omnibus database, and one RNA-seq raw dataset was acquired from The Cancer Genome Atlas (TCGA). Overall, 103 genes were up-regulated and 127 were down-regulated. A protein-protein interaction (PPI) network was established using Cytoscape software, and 12 pivotal genes were selected as hub genes. The 230 differentially expressed genes and 12 hub genes were subjected to functional and pathway enrichment analyses, and the results suggested that cell cycle, nuclear division, mitotic nuclear division, oocyte meiosis, retinol metabolism, and p53 signaling-related pathways play important roles in HBV-related HCC progression. Further, among the 12 hub genes, kinesin family member 11 (KIF11), TPX2 microtubule nucleation factor (TPX2), kinesin family member 20A (KIF20A), and cyclin B2 (CCNB2) were identified as independent prognostic genes by survival analysis and univariate and multivariate Cox regression analysis. These four genes showed higher expression levels in HCC than in normal tissue samples, as identified upon analyses with Oncomine. In addition, in comparison with normal tissues, the expression levels of KIF11, TPX2, KIF20A, and CCNB2 were higher in HBV-related HCC than in HCV-related HCC tissues. In conclusion, our results suggest that KIF11, TPX2, KIF20A, and CCNB2 might be involved in the carcinogenesis and development of HBV-related HCC. They can thus be used as independent prognostic genes and novel biomarkers for the diagnosis of HBV-related HCC and development of pertinent therapeutic strategies.", "claims": [{"id": "claim-method", "statement": "Wilcoxon test was carried out between the HCC and normal tissues.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33193629", "locator": "sections[11] \"Expression Levels of Potential Prognostic Biomarkers in HCV- and HBV-Related HCC\" paragraph 2", "quote": "Wilcoxon test was carried out between the HCC and normal tissues."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data analyzed in this manuscript can be downloaded from the NCBI Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo) using the accession numbers GSE25599, GSE94660, GSE77509, and GSE69715, and TCGA (https://cancergenome.nih.gov/), and the ICGC (https://dcc.icgc.org/releases/current/Projects/LIRI-JP) database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33193629", "locator": "sections[21] \"Data Availability Statement\" paragraph 2", "quote": "The data analyzed in this manuscript can be downloaded from the NCBI Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo) using the accession numbers GSE25599, GSE94660, GSE77509, and GSE69715, and TCGA (https://cancergenome.nih.gov/), and the ICGC (https://dcc.icgc.org/releases/current/Projects/LIRI-JP) database."}], "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:33193629"], "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:GSE25599"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE25599"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33193629", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": 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the NCBI Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo) using the accession numbers GSE25599, GSE94660, GSE77509, and GSE69715, and TCGA (https://cancergenome.nih.gov/), and the ICGC (https://dcc.icgc.org/releases/current/Projects/LIRI-JP) database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data analyzed in this manuscript can be downloaded from the NCBI Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo) using the accession numbers GSE25599, GSE94660, GSE77509, and GSE69715, and TCGA (https://cancergenome.nih.gov/), and the ICGC (https://dcc.icgc.org/releases/current/Projects/LIRI-JP) database.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM629246", "GSM629247", "GSM629248", "GSM629249", "GSM629250", "GSM629251", "GSM629252", "GSM629253", "GSM629254", "GSM629255", "GSM629256", "GSM629257", "GSM629258", "GSM629259", "GSM629260", "GSM629261", 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"taxon": "Homo sapiens", "title": "RNA sequencing (RNA-SEQ) of 21 HBV-HCC patients with non-neoplastic liver and tumor tissues", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33193629:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:263fa8399b8809700b8b6e376bc540d53b43b3e8b38174b3efeb52716dacf33e", "bytes": 1854, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#T1", "version": null, "note": "Univariate and Multivariate COX analysis of hub genes.", "structure": {"pmcid": "PMC7556301", "section_index": 7, "section_title": "Survival Analysis of Hub Genes", "row_count": 14, "column_count": 10}, "table": {"label": "TABLE 1", "caption": "Univariate and Multivariate COX analysis of hub 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