Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35859724", "kind": "science-record", "revision": 4, "content_hash": "sha256:3f097b34d6294a20e2841a2f710ea73c159caa4ead4266bf32f50bb95a2d83ae", "created_at": "2026-11-01T18:14:56Z", "updated_at": "2026-11-01T22:07:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of a Potential Stemness-Associated Biomarker in Hepatocellular Carcinoma.", "doi": "10.1155/2022/1534593", "pmid": "35859724", "authors": ["Yangyang Zhang", "Ruike Zhang", "Lingxiu Zeng", "Haizhou Wang", "Ruyi Peng", "Meng Zhang", "Hailin Zhang", "Zhenwei Yang", "Liping Gao", "Meng Wang", "Jing Liu"], "journal": "Stem cells international", "year": 2022, "abstract": "Background: Cancer stem cells (CSCs) are typically related to metastasis, recurrence, and drug resistance in malignant tumors. However, the biomarker and mechanism of CSCs need further exploration. This study is aimed at comprehensively depicting the stemness characteristics and identify a potential stemness-associated biomarker in hepatocellular carcinoma (HCC).\nMethods: The data of HCC patients from The Cancer Genome Atlas (TCGA) were collected and divided based on the mRNA expression-based stemness index (mRNAsi) in this study. Weighted gene coexpression network analysis (WGCNA) and the protein-protein interaction (PPI) network were performed, and the genes were screened through the Cytoscape software. Then, we constructed a prognostic expression signature using the multivariable Cox analysis and verified using the GEO and ICGC databases. Even more importantly, we used the three-dimensional (3D) fibrin gel to enrich the tumor-repopulating cells (TRCs) to validate the expression of the signature in CSCs by quantitative RT-PCR.\nResults: mRNAsi was significantly elevated in tumor and high-mRNAsi score was associated with poor overall survival in HCC. The positive stemness-associated (blue) module with 737 genes were screened based on WGCNA, and Budding uninhibited by benzimidazoles 1 (BUB1) was identified as the hub gene highly related to stemness in HCC. Then, the prognostic value and stemness characteristics were well validated in the ICGC and GSE14520 cohorts. Further analysis showed the expression of BUB1 was elevated in TRCs.\nConclusion: BUB1, as a potential stemness-associated biomarker, could serve as a therapeutic CSCs-target and predicted the clinical outcomes of patients with HCC.", "claims": [{"id": "claim-method", "statement": "The expression of the hub gene and clinical characteristics were combined to be analyzed using multivariate Cox regression analysis to determine whether the hub gene was an independent risk factor in both the TCGA and ICGC databases.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35859724", "locator": "sections[8] \"2.6. Multivariate Prognosis Model Construction\" paragraph 2", "quote": "The expression of the hub gene and clinical characteristics were combined to be analyzed using multivariate Cox regression analysis to determine whether the hub gene was an independent risk factor in both the TCGA and ICGC databases."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets supporting the conclusions of this article were available in the TCGA database (https://portal.gdc.cancer.gov), ICGC database (http://www.icgc.org), and GEO database (http://www.ncbi.nlm.nih.gov/geo). The raw data supporting the conclusions of this article accompanies are included in the article and supplementary material. Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35859724", "locator": "sections[23] \"Data Availability\" paragraph 2", "quote": "The datasets supporting the conclusions of this article were available in the TCGA database (https://portal.gdc.cancer.gov), ICGC database (http://www.icgc.org), and GEO database (http://www.ncbi.nlm.nih.gov/geo). The raw data supporting the conclusions of this article accompanies are included in the article and supplementary material. Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Multivariate Cox regression analysis showed that BUB1 expression was an independent predictor of overall survival in the TCGA and ICGC cohorts.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "After controlling for other confounding factors, BUB1 expression remained an independent predictor of overall survival (OS) in both the TCGA (HR = 1.36, 95%CI = 1.16–1.6, p < 0.001) (Figure 4(d)) and the ICGC cohorts (HR = 1.2, 95%CI = 1.12–1.3, p < 0.001) (Figure 4(f))."}, "evidence": [{"asset": "source:pmid:35859724", "locator": "sections[19] \"3.6. Prognostic Value of BUB1 in HCC Patients\" paragraph 2", "quote": "After controlling for other confounding factors, BUB1 expression remained an independent predictor of overall survival (OS) in both the TCGA (HR = 1.36, 95%CI = 1.16–1.6, p < 0.001) (Figure 4(d)) and the ICGC cohorts (HR = 1.2, 95%CI = 1.12–1.3, p < 0.001) (Figure 4(f))."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Multivariate Cox regression analysis showed that BUB1 expression was an independent predictor of overall survival in the TCGA and ICGC cohorts.", "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:35859724"], "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:GSE14520"], "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:GSE14520"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35859724", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2022/1534593", "sha256": "sha256:a5965fa2b37a35d21b9759bb4733ac7228885193d1aa0b83a9d0f880382af998", "bytes": 51095, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2022/1534593", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9293570", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE14520", "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=GSE14520", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14520", "version": null, "note": "The datasets supporting the conclusions of this article were available in the TCGA database (https://portal.gdc.cancer.gov), ICGC database (http://www.icgc.org), and GEO database (http://www.ncbi.nlm.nih.gov/geo). The raw data supporting the conclusions of this article accompanies are included in the article and supplementary material. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets supporting the conclusions of this article were available in the TCGA database (https://portal.gdc.cancer.gov), ICGC database (http://www.icgc.org), and GEO database (http://www.ncbi.nlm.nih.gov/geo). The raw data supporting the conclusions of this article accompanies are included in the article and supplementary material. 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No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "bootstrap_mean_difference", "expected_value": 0.001, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. 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