Centromere protein N may be a novel malignant prognostic biomarker for hepatocellular carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33987018", "kind": "science-record", "revision": 7, "content_hash": "sha256:7ad8e9ffab9259ee252ac6631b17ae221a82af38199fc1611ff12e084c902c16", "created_at": "2026-11-01T15:41:35Z", "updated_at": "2026-11-01T22:03:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Centromere protein N may be a novel malignant prognostic biomarker for hepatocellular carcinoma.", "doi": "10.7717/peerj.11342", "pmid": "33987018", "authors": ["Qingqing Wang", "Xiaoyan Yu", "Zhewen Zheng", "Fengxia Chen", "Ningning Yang", "Yunfeng Zhou"], "journal": "PeerJ", "year": 2021, "abstract": "BACKGROUND: Hepatocellular carcinoma (HCC) is one of the deadliest tumors. The majority of HCC is detected in the late stage, and the clinical results for HCC patients are poor. There is an urgent need to discover early diagnostic biomarkers and potential therapeutic targets for HCC.\nMETHODS: The GSE87630 and GSE112790 datasets from the Gene Expression Omnibus (GEO) database were downloaded to analyze the differentially expressed genes (DEGs) between HCC and normal tissues. R packages were used for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses of the DEGs. A Search Tool for Retrieval of Interacting Genes (STRING) database was used to develop a protein-protein interaction (PPI) network, and also cytoHubba, Molecular Complex Detection (MCODE), EMBL-EBI, CCLE, Gene Expression Profiling Interactive Analysis (GEPIA), and Oncomine analyses were performed to identify hub genes. Gene expression was verified with a third GEO dataset, GSE25097. The Cancer Genome Atlas (TCGA) database was used to explore the correlations between the hub genes and clinical indexes of HCC patients. The functions of the hub genes were enriched by gene set enrichment analysis (GSEA), and the biological significance of the hub genes was explored by real-time polymerase chain reaction (qRT-PCR), western blot, immunofluorescence, CCK-8, colony formation, Transwell and flow cytometry assays with loss-of-function experiments in vitro.\nRESULTS: Centromere protein N (CENPN) was screened as a hub gene affecting HCC tumorigenesis. Evaluation by Cox regression showed that a high level of CENPN expression was an independent danger variable for poor prognosis of HCC. GSEA showed that high CENPN expression was linked to the following pathways: liver cancer subclass proliferation, cell cycle, p53 signaling pathway, Rb1 pathway, positive regulation of cell cycle G1/S phase transition, and DNA damage response signal transduction by p53 class moderators. Further cell experiments showed that knocking down CENPN expression decreased the proliferation and colony-forming abilities of HepG2 and Huh7 cells as well as Ki67 expression in these cell lines. The cell cycle was arrested in G1 phase, which is consistent with previous experiments on CENPN downregulation., but neither migration nor invasion were significantly affected. Western blot results revealed that the expression of p53, p27, p21, CDK4, cyclin D1, CDK2, cyclin E, pRb, E2F1 and c-myc decreased after CENPN knockdown, but there was no significant change in total Rb levels. In addition, CENPN-knockdown cells subjected to irradiation showed significantly enhanced of γ-H2AX expression and reduced colony formation.\nCONCLUSION: CENPN functions as an oncogene in HCC and may be a therapeutic target and promising prognostic marker for HCC.", "claims": [{"id": "claim-method", "statement": "The relationships between variables and patient survival were analyzed with Cox models, and the results were evaluated with SPSS 22.0 software (SPSS, Chicago, IL, United States). CENPN gene expression in the TCGA liver cancer database (TCGA-LIHC) was extracted.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33987018", "locator": "sections[18] \"Statistical analysis\" paragraph 2", "quote": "The relationships between variables and patient survival were analyzed with Cox models, and the results were evaluated with SPSS 22.0 software (SPSS, Chicago, IL, United States)."}, {"asset": "source:pmid:33987018", "locator": "sections[8] \"Database analysis of the differential expression and prognosis of the CENPN gene\" paragraph 2", "quote": "CENPN gene expression in the TCGA liver cancer database (TCGA-LIHC) was extracted."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nThe main data are available at TCGA and NCBI-GEO (GSE87630, GSE112790 and GSE25097). The raw measurements are available in the Supplementary Files.\nhttps://portal.gdc.cancer.gov/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33987018", "locator": "sections[40] \"Data Availability Statement\" paragraphs 1-4", "quote": "The following information was supplied regarding data availability:\nThe main data are available at TCGA and NCBI-GEO (GSE87630, GSE112790 and GSE25097). The raw measurements are available in the Supplementary Files.\nhttps://portal.gdc.cancer.gov/."}], "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:33987018"], "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:GSE112790"], "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:GSE112790"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33987018", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.11342", "sha256": "sha256:8bf07794ffbba4ec3e146d01e3b90cc324cc185765512f3e7eba051a3b5f2f0e", "bytes": 61794, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.11342", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8101454", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE112790", "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=GSE112790", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE112790", "version": null, "note": "The following information was supplied regarding data availability:\nThe main data are available at TCGA and NCBI-GEO (GSE87630, GSE112790 and GSE25097). The raw measurements are available in the Supplementary Files.\nhttps://portal.gdc.cancer.gov/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:\nThe main data are available at TCGA and NCBI-GEO (GSE87630, GSE112790 and GSE25097). 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Cells were cultured in DMEM supplemented with 10% fetal bovine seru", "d cell transfection The human HCC cell lines HepG2 and Huh7 were purchased from Procell Life Sc"], "order_basis": "paper_text_order:2164", "id": "assay:5"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["E, pRb, E2F1 and c-myc decreased after CENPN knockdown, but there was no significant change in tota", "hange in total Rb levels. In addition, CENPN-knockdown cells subjected to irradiation showed signif", "Ritchie et al., 2015). 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