Exploration and Validation of Key Genes and Immune Infiltration in Alcoholic Hepatitis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40589609", "kind": "science-record", "revision": 3, "content_hash": "sha256:2ffea62eae182ea240a130f744e0cffff8577d3c06e891c1c2a7a777c4315a17", "created_at": "2026-11-01T20:30:40Z", "updated_at": "2026-11-01T22:14:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploration and Validation of Key Genes and Immune Infiltration in Alcoholic Hepatitis.", "doi": "10.2147/JIR.S514515", "pmid": "40589609", "authors": ["Yingna Mei", "Yitao Zheng", "Xingfen Zhang", "Ting Hu", "Xiaoqing Zheng", "Cui Zhang", "Qinzhi Deng"], "journal": "Journal of inflammation research", "year": 2025, "abstract": "Objective: Apart from alcohol abstinence and glucocorticoids, there is still no effective treatment to improve alcoholic hepatitis, and the specific mechanism of its pathogenesis is still unclear.\nMethods: We screened the differential genes in GEO alcoholic hepatitis database by differential analysis and screened the eQTL genes that have causal relationship with alcoholic hepatitis by Mendelian randomization analysis. The intersection of differential genes and eQTL genes was used to obtain candidate genes. The candidate genes were then screened out by machine learning, and their expression was further verified in clinical patients and mice with alcoholic hepatitis. Based on key genes, pathway analysis via single-gene GSEA analysis and immune microenvironment analysis via ssGSEA analysis were conducted to explore the relationship between key genes and immune microenvironment. Finally, regulatory relationship between key genes and immune cells was explored based on cell experiments.\nResults: Based on the GEO Alcoholic hepatitis database (GSE28619 and GSE142530) and Mendelian randomization of eQTL genes, we obtained 17 candidate genes. We then obtained two key genes (CXCL8 and CTNNA1) through lasso and random forest tree algorithms. CXCL8 and CTNNA1 were highly expressed in the alcoholic hepatitis group, which were verified in clinical patients and mice. Through single-gene GSEA analysis, two key genes were identified to be enriched in the antigen presentation pathway. At the same time, the alcoholic hepatitis group had obvious immune infiltration disorder, and two key genes were correlated with immune environment via correlation analysis. B cells and NKT cells exhibited the highest correlation with key genes. In alcoholic hepatitis mice, liver infiltration of B cells and NKT cells was verified. Through cell experiments, ethanol exposure increased CTNNA1 and CXCL8 expression in NKT and B cells, enhancing inflammatory cytokine release and suppressing IgG production, respectively. Silencing CXCL8 and CTNNA1 reversed these effects.\nConclusion: These results suggested that CXCL8 and CTNNA1 were potential biomarkers for alcoholic hepatitis, and might be new targets for the treatment of alcoholic hepatitis.", "claims": [{"id": "claim-method", "statement": "Using Pearson correlation analysis test the relationship between the key genes and immune microenvironment.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40589609", "locator": "sections[11] \"Comparison of the Immune Microenvironment Between AH and Normal Groups\" paragraph 2", "quote": "Using Pearson correlation analysis test the relationship between the key genes and immune microenvironment."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE28619 (15 AH vs 7 control), GSE142530 (13 AH vs 16 control) and GSE155907 (5 AH vs 4 control) datasets were downloaded from the Gene Expression Omnibus database, and sequenced using the GPL570, GLP11154 and GPL21290 platforms.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40589609", "locator": "sections[3] \"Data Acquisition\" paragraph 2", "quote": "The GSE28619 (15 AH vs 7 control), GSE142530 (13 AH vs 16 control) and GSE155907 (5 AH vs 4 control) datasets were downloaded from the Gene Expression Omnibus database, and sequenced using the GPL570, GLP11154 and GPL21290 platforms."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Two key genes, CXCL8 and CTNNA1, were obtained through lasso and random forest tree algorithms.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40589609", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We then obtained two key genes (CXCL8 and CTNNA1) through lasso and random forest tree algorithms."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Two key genes, CXCL8 and CTNNA1, were obtained through lasso and random forest tree algorithms.", "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:40589609"], "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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Two cell lines were cultured in 1640 medium supplemented with 10% fetal b", "FUHENG BIOLOGY (FH1258). Two cell lines were cultured in 1640 medium supplemented with 10% fetal bovi"], "order_basis": "paper_text_order:4045", "id": "assay:1"}, {"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": ["as treated for 24h.28 After that, cells were transfected with siRNAs (siCXCL8 and siCTNNA1) (General", "for subsequent experiments. The sequence of siRNA primers was shown in Table 1.Table 1Sequence"], "order_basis": "paper_text_order:4399", "id": "assay:2"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["c Hepatitis Patients and Mice We applied the Elisa assay to evaluate CXCL8 and CTNNA1 levels in"], "order_basis": "paper_text_order:5109", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ssfully constructed. CXCL8 was not expressed in mice. It has been reported that CXCL2 in mice cou", "sed in mice. It has been reported that CXCL2 in mice could replace CXCL8 in humans.29 Thus, we ap", "evaluated the expression of CXCL2 and CTNNA1 in mice liver. CTNNA1 and CXCL2 levels were increase"], "order_basis": "paper_text_order:6414", "id": "assay:4"}, {"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": ["replace CXCL8 in humans.29 Thus, we applied immunohistochemical staining to evaluated the expression of CXCL"], "order_basis": "paper_text_order:6514", "id": "assay:5"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Using Pearson correlation analysis test the relationship between the key genes and immune microenvironment."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}