Role for ubiquitin-specific protease 7 (USP7) in the treatment and the immune response to hepatocellular carcinoma: potential mechanisms.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38130306", "kind": "science-record", "revision": 2, "content_hash": "sha256:7a3d7aa1a4e5eeb7e40539b3cc5206cbd739ada6451ded0d4536bcd48a85aea8", "created_at": "2026-11-01T19:20:03Z", "updated_at": "2026-11-01T21:32:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Role for ubiquitin-specific protease 7 (USP7) in the treatment and the immune response to hepatocellular carcinoma: potential mechanisms.", "doi": "10.21037/tcr-23-153", "pmid": "38130306", "authors": ["Huiwen Ying", "Bin Zhang", "Guilian Cao", "Yunan Wang", "Xian Zhang"], "journal": "Translational cancer research", "year": 2023, "abstract": "Background: Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that can affect or regulate a variety of cellular activities. The purpose of this study was to investigate therapeutic and immunologic effects of USP7 in hepatocellular carcinoma (HCC), and as well to evaluate potential mechanisms of action.\nMethods: USP7-related gene expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) dataset, International Cancer Genome Consortium (ICGC) dataset, and Gene Expression Omnibus (GEO) dataset. Pathways associated with USP7 were determined by gene set enrichment analysis (GSEA). The relationships among USP7, immunity, and drug therapy were also investigated and potential mechanisms of action were explored.\nResults: TCGA database results demonstrated USP7 mRNA expression levels to be upregulated in HCC tissues. Results were validated with UALCAN, ICGC, and GSE10143 datasets, as well as immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) experiments and were consistent with TCGA database findings (all P<0.05). GSEA analysis demonstrated increased USP7 levels to be associated with CHEMOKINE, Janus kinase/signal transducer and activator of transcription (JAK-STAT), mitogen-activated protein kinase (MAPK), P53, vascular endothelial growth factor (VEGF), and wingless (WNT) signaling pathways. Based on immune correlation analysis, USP7 was dramatically associated with immune cells and immune checkpoint molecules. In terms of drug therapy, USP7 expression levels were significantly related to HCC sensitivity to ciclosporin, talazoparib, dabrafenib, trametinib, paclitaxel, sorafenib, bortezomib, sunitinib, and crizotinib. Based on these results, we mechanistically propose an association between USP7 and these four drug targets: B-Raf proto-oncogene serine/threonine protein kinase (BRAF), mitogen-activated extracellular signal-regulated kinase (MEK), DNA topoisomerase I (TOPOI), and poly ADP-ribose polymerase (PARP).\nConclusions: USP7 plays a therapeutic and immunological role in HCC. The four drug targets BRAF, MEK, TOPOI, and PARP are implicated in the USP7 mechanism of action.", "claims": [{"id": "claim-method", "statement": "We assessed the HCC diagnostic value of USP7 by receiver operating characteristic (ROC) analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38130306", "locator": "sections[9] \"USP7 expression and diagnostic value for HCC\" paragraph 2", "quote": "We assessed the HCC diagnostic value of USP7 by receiver operating characteristic (ROC) analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-153/dss", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38130306", "locator": "sections[21] \"Footnotes\" paragraph 2", "quote": "Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-153/dss"}], "state": "complete"}, {"id": "claim-target-result", "statement": "USP7 mRNA expression was significantly higher in HCC tumor tissues than in normal tissues.", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "The bar chart demonstrates USP7 expression to be observably higher in HCC tumors than in normal tissues (P<0.001; Figure 1B)."}, "evidence": [{"asset": "source:pmid:38130306", "locator": "sections[9] \"USP7 expression and diagnostic value for HCC\" paragraph 2", "quote": "The bar chart demonstrates USP7 expression to be observably higher in HCC tumors than in normal tissues (P<0.001; Figure 1B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "USP7 mRNA expression was significantly higher in HCC tumor tissues than in normal tissues.", "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:38130306"], "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. 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