Ubiquitin D Correlates with Disease Severity and T Cell Infiltration in Cholestasis: Evidence from Integrated Bioinformatics and Experimental Analyses.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41399364", "kind": "science-record", "revision": 4, "content_hash": "sha256:c31a2f60ccb46a2426bde5e50b78690429199aff59060d6de91b24bb84088fbf", "created_at": "2026-11-01T20:31:24Z", "updated_at": "2026-11-01T22:57:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Ubiquitin D Correlates with Disease Severity and T Cell Infiltration in Cholestasis: Evidence from Integrated Bioinformatics and Experimental Analyses.", "doi": "10.7150/ijms.122687", "pmid": "41399364", "authors": ["Huiwen Wang", "Jian Zhang", "Xun Huang", "Shifang Peng"], "journal": "International journal of medical sciences", "year": 2026, "abstract": "Cholestasis is a complex pathophysiological syndrome characterized by impaired bile secretion and excretion. Extensive research has revealed that Ubiquitin D (UBD) plays a pivotal role in numerous types of malignancies and benign diseases. However, the underlying involvement of UBD in cholestasis remains unclear. The aim of this study was to analyze the role of UBD in Cholestasis. Transcriptome data from cholestasis patients (GSE61260, GSE159676 and GSE183754) were obtained from the Gene Expression Omnibus (GEO) database. These datasets, along with cholestatic mouse models and clinical specimens, were utilized to evaluate hepatic UBD expression. Subsequently, immunohistochemistry and immunofluorescence staining were applied to validate the expression and localization of hepatic UBD. Moreover, the association of hepatic UBD levels with clinical parameters was evaluated using Pearson's correlation analysis. In addition, Gene set enrichment analysis (GSEA) and xCell were employed to investigate the immune-related signatures and immune cell infiltration link to UBD in cholestasis, with findings further validated through immunofluorescence staining. Finally, the association of the hepatic UBD with T cell-related chemokine and chemokine receptor was explored using Pearson's correlation analysis. The results showed that UBD was significantly and consistently upregulated in the livers across cholestasis patient transcriptomic data, experimental mouse models, and clinical specimens. Hepatic UBD levels positively correlate with the severity of cholestasis and hepatocytes are identified as the primary source of UBD in cholestatic livers. Functional enrichment analysis indicated that immune-related pathway was significantly activated in the cholestatic liver with high expression of UBD group. Moreover, hepatic UBD expression was positively associated with the infiltration of T cells and with the expression of T cell-related chemokines and chemokine receptors in cholestasis. In conclusion, UBD is a key gene associated with disease severity and T cells infiltration in cholestasis. These findings provide new insight into the key biomarker of cholestasis and further highlight that UBD might be a promising novel therapeutic target for patients with cholestasis.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) were identified using either the “limma” or DESeq2 package in R, with statistical significance defined as an adjusted p-value < 0.05 and | log2 fold change (FC) | ≥ 1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41399364", "locator": "sections[3] \"Data acquisition and identification of differentially expressed genes\" paragraph 2", "quote": "Differentially expressed genes (DEGs) were identified using either the “limma” or DESeq2 package in R, with statistical significance defined as an adjusted p-value < 0.05 and | log2 fold change (FC) | ≥ 1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Liver transcriptome datasets GSE61260, GSE159676, and GSE183754 for this study can be found in the GEO (http://www.ncbi.nlm.nih.gov/geo). Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41399364", "locator": "sections[27] \"Availability of data and materials\" paragraph 2", "quote": "Liver transcriptome datasets GSE61260, GSE159676, and GSE183754 for this study can be found in the GEO (http://www.ncbi.nlm.nih.gov/geo). 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These datasets, along with cholestatic mouse models and clinical specimens, were utilized", "is patient transcriptomic data, experimental mouse models, and clinical specimens. Hepatic UBD", "imal experiments Eight-week-old male C57BL/6 mice were purchased from the Hunan Slake Jingda Labora", "lake Jingda Laboratory Animals Co., Ltd. All mice were housed under specific pathogen-free (SPF) co"], "order_basis": "paper_text_order:674", "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": 0.99, "evidence": ["aluate hepatic UBD expression. Subsequently, immunohistochemistry and immunofluorescence staining were applied", "sion. Subsequently, immunohistochemistry and immunofluorescence staining were applied to validate the expres", "sis, with findings further validated through immunofluorescence staining. Finally, the association of the he", "asis. ****p < 0.0001. UBD, Ubiquitin D; IHC, immunohistochemistry; HC, healthy control; PBC, primary biliary c"], "order_basis": "paper_text_order:775", "id": "assay:2"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Differentially expressed genes (DEGs) were identified using either the “limma” or DESeq2 package in R, with statistical significance defined as an adjusted p-value < 0.05 and | log2 fold change (FC) | ≥ 1."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}