Identification and Validation of Ubiquitin-Specific Proteases as a Novel Prognostic Signature for Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33718205", "kind": "science-record", "revision": 6, "content_hash": "sha256:2eb08d2515ef147e6869f52b395859938ed3624684d94773161c431ec8ca55cd", "created_at": "2026-11-01T15:41:28Z", "updated_at": "2026-11-01T21:24:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of Ubiquitin-Specific Proteases as a Novel Prognostic Signature for Hepatocellular Carcinoma.", "doi": "10.3389/fonc.2021.629327", "pmid": "33718205", "authors": ["Wenkai Ni", "Saiyan Bian", "Mengqi Zhu", "Qianqian Song", "Jianping Zhang", "Mingbing Xiao", "Wenjie Zheng"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "PURPOSE: Ubiquitin-specific proteases (USPs), as a sub-family of deubiquitinating enzymes (DUBs), are responsible for the elimination of ubiquitin-triggered modification. USPs are recently correlated with various malignancies. However, the expression features and clinical significance of USPs have not been systematically investigated in hepatocellular carcinoma (HCC).\nMETHODS: Genomic alterations and expression profiles of USPs were investigated in CbioPortal and The Cancer Genome Atlas (TCGA) Liver hepatocellular carcinoma (LIHC) dataset. Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were conducted to establish a risk signature for HCC prognosis in TCGA LIHC cohort. Subsequently, Kaplan-Meier analysis, receiver operating characteristic (ROC) curves and univariate/multivariate analyses were performed to evaluate the prognostic significance of the risk signature in TCGA LIHC and international cancer genome consortium (ICGC) cohorts. Furthermore, we explored the alterations of the signature genes during hepatocarcinogenesis and HCC progression in GSE89377. In addition, the expression feature of USP39 was further explored in HCC tissues by performing western blotting and immunohistochemistry.\nRESULTS: Genomic alterations and overexpression of USPs were observed in HCC tissues. The consensus analysis indicated that the USPs-overexpressed sub-Cluster was correlated with aggressive characteristics and poor prognosis. Cox regression with LASSO algorithm identified a risk signature formed by eight USPs for HCC prognosis. High-risk group stratified by the signature score was correlated with advanced tumor stage and poor survival HCC patients in TCGA LIHC cohort. In addition, the 8-USPs based signature could also robustly predict overall survival of HCC patients in ICGC(LIRI-JP) cohort. Furthermore, gene sets enrichment analysis (GSEA) showed that the high-risk score was associated with tumor-related pathways. According to the observation in GSE89377, USP39 expression was dynamically increased with hepatocarcinogenesis and HCC progression. The overexpression of USP39 was further determined in a local HCC cohort and correlated with poor prognosis. The co-concurrence analysis suggested that USP39 might promote HCC by regulating cell-cycle- and proliferation- related genes.\nCONCLUSION: The current study provided a USPs-based signature, highlighting its robust prognostic significance and targeted value for HCC treatment.", "claims": [{"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33718205", "locator": "sections[26] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "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:33718205"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33718205", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2021.629327", "sha256": 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ICGC.", "structure": {"pmcid": "PMC7949004", "section_index": 4, "section_title": "Data Acquisition and Preprocessing", "row_count": 40, "column_count": 3}, "table": {"label": "Table 1", "caption": "The clinical characteristic information of the HCC patients in TCGA and ICGC.", "rows": [["Characteristics", "TCGA(%)", "ICGC (%)"], ["Number of Patients", "374", "232"], ["Age"], ["<60", "177 (47.32)", "64(27.59)"], ["≥60", "196(52.41)", "168(72.41)"], ["NA", "1(0.27)", "NA"], ["Gender"], ["Male", "253(67.65)", "171 (73.71)"], ["Female", "121(32.35)", "61 (26.29)"], ["Survival status"], ["Alive", "238(63.64)", "189(81.47)"], ["Dead", "130(34.76)", "43 (18.53)"], ["NA", "6(1.60)", "NA"], ["Stage"], ["I", "173(46.26)", "36(15.52)"], ["II", "87(23.26)", "106(45.69)"], ["III", "85(22.73)", "71(30.60)"], ["IV", "5(1.34)", "19(8.19)"], ["NA", "24(6.42)", "NA"], ["Histological grade"], ["G1", "55(14.71)", "NA"], ["G2", "178(47.59)", "NA"], ["G3", "124(33.16)", "NA"], ["G4", "12(3.21)", "NA"], 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USPs.", "structure": {"pmcid": "PMC7949004", "section_index": 15, "section_title": "The Expression Features of USPs in HCC", "row_count": 23, "column_count": 6}, "table": {"label": "Table 2", "caption": "GO_BP and KEGG analyses of the liver-specific interaction of USPs.", "rows": [["Pathway", "Total", "Expected", "Hits", "P Value", "FDR"], ["GO_BP analysis"], ["Cellular protein catabolic process", "518", "25.6", "114", "5.77E-44", "4.73E-41"], ["Protein catabolic process", "644", "31.8", "121", "3.12E-39", "1.28E-36"], ["Cellular macromolecule catabolic process", "849", "42", "138", "1.44E-37", "3.92E-35"], ["Macromolecule catabolic process", "1070", "52.9", "148", "4.12E-32", "6.76E-30"], ["Proteolysis", "1100", "54.1", "133", "3.10E-23", "4.24E-21"], ["Protein modification", "713", "35.2", "96", "8.08E-20", "9.47E-18"], ["Protein ubiquitination", "658", "32.5", "88", "5.17E-18", "5.30E-16"], ["Cellular catabolic process", "2140", "106", "189", "7.86E-17", "7.16E-15"], ["Catabolic 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RESULTS: Genomic a", "angsu, China) in 2018, which were frozen for western blotting. Liver specimens were collected from 106 pat"], "order_basis": "paper_text_order:1283", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["C tissues by performing western blotting and immunohistochemistry. RESULTS: Genomic alterations and overexpres"], "order_basis": "paper_text_order:1304", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["Kaplan-Meier"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}