Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36051101", "kind": "science-record", "revision": 5, "content_hash": "sha256:acfe8e416d280540778a1d3cb357008b2cc12657ab68064b1f3a8a5a61328d20", "created_at": "2026-11-01T18:15:13Z", "updated_at": "2026-11-01T22:49:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis.", "doi": "10.4251/wjgo.v14.i7.1265", "pmid": "36051101", "authors": ["Yue Li", "Shou-Li Yuan", "Jing-Ya Yin", "Kun Yang", "Xin-Gang Zhou", "Wen Xie", "Qi Wang"], "journal": "World journal of gastrointestinal oncology", "year": 2022, "abstract": "BACKGROUND: Liver fibrosis and hepatocellular carcinoma (HCC) are common adverse consequences of chronic liver injury. The interaction of various risk factors may cause them to happen. Identification of specific biomarkers is of great significance for understanding the occurrence, development mechanisms, and determining the novel tools for diagnosis and treatment of both liver fibrosis and HCC.\nAIM: To identify liver fibrosis-related core genes, we analyzed the differential expression pattern of core genes in liver fibrosis and HCC.\nMETHODS: Gene expression profiles of three datasets, GSE14323, GSE36411, and GSE89377, obtained from the Gene Expression Omnibus (GEO) database, were analyzed, and differentially expressed genes (DEGs) between patients with liver cirrhosis and healthy controls were identified by screening via R software packages and online tool for Venn diagrams. The WebGestalt online tool was used to identify DEGs enriched in biological processes, molecular functions, cellular components, and Kyoto Encyclopedia of Genes and Genomes pathways. The protein-protein interactions of DEGs were visualized using Cytoscape with STRING. Next, the expression pattern of core genes was analyzed using Western blot and immunohistochemistry in a carbon tetrachloride (CCl4)-induced liver cirrhosis mouse model and in patient liver samples. Finally, Kaplan-Meier curves were constructed using the Kaplan-Meier plotter online server.\nRESULTS: Forty-five DEGs (43 upregulated and 2 downregulated genes) associated with liver cirrhosis were identified from three GEO datasets. Ten hub genes were identified, which were upregulated in liver cirrhosis. Western blot and immunohistochemical analyses of the three core genes, decorin (DCN), dermatopontin (DPT), and SRY-box transcription factor 9 (SOX9), revealed that they were highly expressed in the CCl4-induced liver cirrhosis mouse model. The expression levels of DCN and SOX 9 were positively correlated with the degree of fibrosis, and SOX 9 level in HCC patients was significantly higher than that in fibrosis patients. However, high expression of DPT was observed only in patients with liver fibrosis, and its expression in HCC was low. The gene expression profiling interactive analysis server (GEPIA) showed that SOX9 was significantly upregulated whereas DCN and DPT were significantly downregulated in patients with HCC. In addition, the Kaplan-Meier curves showed that HCC patients with higher SOX9 expression had significantly lower 5-year survival rate, while patients with higher expression of DCN or DPT had significantly higher 5-year survival rates.\nCONCLUSION: The expression levels of DCN, DPT, and SOX9 were positively correlated with the degree of liver fibrosis but showed different correlations with the 5-year survival rates of HCC patients.", "claims": [{"id": "claim-method", "statement": "DEGs between the cirrhosis and healthy liver tissue groups were identified using limma package by limiting the value of adjustment: P-value (adjust. P < 0.05) and the absolute value of logFC (|logFC| > 1.2 or 0.6).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36051101", "locator": "sections[9] \"Microarray and gene expression analysis\" paragraph 2", "quote": "DEGs between the cirrhosis and healthy liver tissue groups were identified using limma package by limiting the value of adjustment: P-value (adjust. P < 0.05) and the absolute value of logFC (|logFC| > 1.2 or 0.6)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study, which can be found here: GSE14323, GSE36411 and GSE89377. Technical appendix, statistical code, and data set available from the corresponding author at wangqidl04@ccmu.edu.cn. No additional data are available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36051101", "locator": "sections[32] \"Data sharing statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study, which can be found here: GSE14323, GSE36411 and GSE89377. Technical appendix, statistical code, and data set available from the corresponding author at wangqidl04@ccmu.edu.cn. No additional data are available."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using three GEO datasets, the study identified 45 DEGs associated with cirrhosis and 10 hub genes, with DCN, DPT, and SOX9 further validated as fibrosis-related genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36051101", "locator": "sections[15] \"Identification of DEGs\" paragraph 2", "quote": "Using Venn diagram online tool, we identified 45 DEGs (43 upregulated genes and 2 downregulated genes) associated with cirrhosis from the three datasets (Figure 1D, Table 1)."}, {"asset": "source:pmid:36051101", "locator": "sections[17] \"PPI network construction and identification of hub genes\" paragraph 2", "quote": "The top 10 hub genes were identified using the CytoHubba plugin of Cytoscape, which included C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, C-X-C motif chemokine receptor 4 (CXCR4), DCN, DPT, laminin subunit alpha 2 (LAMA2), lumican (LUM), microfibril associated protein 4 (MFAP4), platelet-derived growth factor receptor alpha (PDGFRA), and SOX9 (Figure 1F)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Using three GEO datasets, the study identified 45 DEGs associated with cirrhosis and 10 hub genes, with DCN, DPT, and SOX9 further validated as fibrosis-related genes.", "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:36051101"], "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:36051101", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.4251/wjgo.v14.i7.1265", "sha256": "sha256:c32984ba385509302db3f78506886c01d3094433c394e67f0ec8c97f91e0b0af", "bytes": 36894, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.4251/wjgo.v14.i7.1265", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9305567", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "DEGs between the cirrhosis and healthy liver tissue groups were identified using limma package by limiting the value of adjustment: P-value (adjust. 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Western blot and immunohistochemical analyses of the three core genes, decorin (D", "ular carcinoma (HCC) groups were analyzed by immunohistochemistry. The H&E staining and Masson’s trichrome sta"], "order_basis": "paper_text_order:74", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ion pattern of core genes was analyzed using Western blot and immunohistochemistry in a carbon tetrach", ", which were upregulated in liver cirrhosis. 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