Screening and identification of key genes between liver hepatocellular carcinoma (LIHC) and cholangiocarcinoma (CHOL) by bioinformatic analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33327311", "kind": "science-record", "revision": 7, "content_hash": "sha256:78f119f4495448978ee82d98917b2563aa32b70c3dbf88485d9a6b09fbd804f5", "created_at": "2026-11-01T15:41:19Z", "updated_at": "2026-11-01T22:02:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Screening and identification of key genes between liver hepatocellular carcinoma (LIHC) and cholangiocarcinoma (CHOL) by bioinformatic analysis.", "doi": "10.1097/MD.0000000000023563", "pmid": "33327311", "authors": ["Xindan Kang", "Li Bai", "Xiaoguang Qi", "Jing Wang"], "journal": "Medicine", "year": 2020, "abstract": "BACKGROUND: Liver hepatocellular carcinoma (LIHC) and cholangiocarcinoma (CHOL) are common primary liver cancers worldwide. Liver stem cells have biopotential to differentiate into either hepatocytes and cholangiocytes, the phenotypic overlap between LIHC and CHOL has been acceptable as a continuous liver cancer spectrum. However, few studies directly investigated the underlying molecular mechanisms between LIHC and CHOL.\nMETHOD: To identify the candidate genes between LIHC and CHOL, three data series including GSE31370, GSE15765 and GSE40367 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape.\nRESULTS: A total of 171 DEGs were identified, consisting of 49 downregulated genes and 122 upregulated genes. Compared with CHOL, the enriched functions of the DEGs mainly included steroid metabolic process, acute inflammatory response, coagulation. Meanwhile, the pathway of KEGG enrichment analyses showed that the upregulated gene(s) were mainly enriched complement and coagulation cascades, cholesterol metabolism and PPAR signaling pathway, while the downregulated gene(s) were mainly enriched in ECM-receptor interaction, focal adhesion, bile secretion. Similarly, the most significant module was identified and biological process analysis revealed that these genes were mainly enriched in regulation of blood coagulation, acute inflammatory response, complement and coagulation cascades. Finally, two (ITIH2 and APOA2) of 10 hub genes had been screened out to help differential diagnosis.\nCONCLUSION: 171 DEGs and two (ITIH2 and APOA2) of 10 hub genes identified in the present study help us understand the different molecular mechanisms between LIHC and CHOL, and provide candidate targets for differential diagnosis.", "claims": [{"id": "claim-data-access", "statement": "Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33327311", "locator": "sections[16] \"fn-group\" paragraph 1", "quote": "Data sharing not applicable to this article as no datasets were generated or analyzed during the current study."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:33327311"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE15765"], "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": ["data:geo:GSE15765"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33327311", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1097/MD.0000000000023563", "sha256": 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{"label": "Table 1", "caption": "Statistics of 3 data series derived from GEO database.", "rows": [["GEO series", "CHOL", "LIHC", "Total", "Tissue source"], ["GSE31370", "6", "15", "26", "liver"], ["GSE15765", "13", "70", "90", "liver"], ["GSE40367", "4", "15", "61", "liver"]], "row_count": 4, "column_count": 5, "numeric_cells": 12, "header_rows": 1, "locator": "section[3]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33327311:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:47ed48af522eea6064d269aeeeb2c4a76544253df2ce486c72df55c1267ff3c8", "bytes": 1608, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#T3", "version": null, "note": "GO and KEGG pathway enrichment analysis of DEGs in the most significant module.", "structure": {"pmcid": "PMC7738106", "section_index": 6, "section_title": "PPI network construction and module analysis", "row_count": 20, "column_count": 5}, "table": {"label": "Table 3", "caption": "GO and KEGG pathway enrichment analysis of DEGs in the most significant module.", "rows": [["Category", "Term", "Pathway description", "Count in gene set", "Adjusted P"], ["BP term", "GO:0009611", "response to wounding", "16", "1.06E-11"], ["BP term", "GO:0030193", "regulation of blood coagulation", "8", "2.04E-10"], ["BP term", "GO:0050818", "regulation of coagulation", "8", "3.64E-10"], ["BP term", "GO:0032101", "regulation of response to external stimulus", "10", "3.43E-09"], ["BP term", "GO:0042060", "wound healing", "10", "1.43E-08"], ["BP term", "GO:0006953", "acute-phase response", "7", "1.91E-08"], ["BP term", "GO:0030195", "negative regulation of blood coagulation", "6", "8.61E-08"], ["BP term", "GO:0002526", "acute inflammatory response", "8", "7.76E-08"], ["BP term", "GO:0050817", "coagulation", "8", "9.16E-08"], ["BP term", "GO:0007596", "blood coagulation", "8", "9.16E-08"], ["BP term", "GO:0050819", "negative regulation of coagulation", "6", "1.17E-07"], ["BP term", "GO:0007599", "hemostasis", "8", "1.12E-07"], ["CC term", "GO:0005615", "extracellular space", "29", "5.54E-20"], ["CC term", "GO:0005576", "extracellular region", "22", "1.77E-19"], ["CC term", "GO:0044421", "extracellular region part", "22", "1.29E-16"], ["MF term", "GO:0004857", "enzyme inhibitor activity", "14", "3.38E-13"], ["MF term", "GO:0004866", "endopeptidase inhibitor activity", "12", "2.47E-13"], ["MF term", "GO:0030414", "peptidase inhibitor activity", "12", "2.99E-13"], ["KEGG pathway", "hsa04610", "Complement and coagulation cascades", "10", "4.97E-14"]], "row_count": 20, "column_count": 5, "numeric_cells": 57, "header_rows": 1, "locator": "section[11]/table-wrap[1]#T3"}}, {"id": "asset:table:pmid:33327311:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:5ef203f3149922ea3e8be840e527732d1274453d955d74a2d4a38005c531e5bb", "bytes": 1641, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#T2", "version": null, "note": "GO analysis of DEGs between LIHC and CHOL.", "structure": {"pmcid": "PMC7738106", "section_index": 10, "section_title": "GO term and KEGG pathway enrichment analyses of the common DEGs", "row_count": 22, "column_count": 5}, "table": {"label": "Table 2", "caption": "GO analysis of DEGs between LIHC and CHOL.", "rows": [["Category", "Term", "Pathway description", "Count in gene set", "Adjusted P"], ["Upregulated"], ["BP term", "GO:0008202", "steroid metabolic process", "19", "4.58E-11"], ["BP term", "GO:0009611", "response to wounding", "25", "2.68E-09"], ["BP term", "GO:0016125", "sterol metabolic process", "13", "1.25E-08"], ["BP term", "GO:0008203", "cholesterol metabolic process", "12", "6.16E-08"], ["BP term", "GO:0002526", "acute inflammatory response", "12", "9.87E-08"], ["BP term", "GO:0032101", "regulation of response to external stimulus", "14", "1.04E-07"], ["BP term", "GO:0042060", "wound healing", "14", "8.55E-07"], ["BP term", "GO:0007596", "blood coagulation", "11", "1.55E-06"], ["BP term", "GO:0050817", "coagulation", "11", "1.55E-06"], ["BP term", "GO:0030193", "regulation of blood coagulation", "8", "1.97E-06"], ["CC term", "GO:0005615", "extracellular space", "33", "1.17E-13"], ["CC term", "GO:0005576", "extracellular region", "50", "2.31E-11"], ["CC term", "GO:0044421", "extracellular region part", "33", "3.88E-10"], ["MF term", "GO:0004866", "endopeptidase inhibitor activity", "13", "8.73E-07"], ["MF term", "GO:0004867", "serine-type endopeptidase inhibitor activity", "11", "7.23E-07"], ["MF term", "GO:0030414", "peptidase inhibitor activity", "13", "5.38E-07"], ["MF term", "GO:0004857", "enzyme inhibitor activity", "16", "4.87E-07"], ["downregulated", "", "", "", ""], ["CC term", "GO:0005887", "integral to plasma membrane", "12", "0.043720371"], ["CC term", "GO:0031226", "intrinsic to plasma membrane", "12", "0.035406774"]], "row_count": 22, "column_count": 5, "numeric_cells": 57, "header_rows": 1, "locator": "section[10]/table-wrap[1]#T2"}}, {"id": "asset:table:pmid:33327311:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:47ed48af522eea6064d269aeeeb2c4a76544253df2ce486c72df55c1267ff3c8", "bytes": 1608, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#T3", "version": null, "note": "GO and KEGG pathway enrichment analysis of DEGs in the most significant module.", "structure": {"pmcid": "PMC7738106", "section_index": 11, "section_title": "PPI network construction and module analysis", "row_count": 20, "column_count": 5}, "table": {"label": "Table 3", "caption": "GO and KEGG pathway enrichment analysis of DEGs in the most significant module.", "rows": [["Category", "Term", "Pathway description", "Count in gene set", "Adjusted P"], ["BP term", "GO:0009611", "response to wounding", "16", "1.06E-11"], ["BP term", "GO:0030193", "regulation of blood coagulation", "8", "2.04E-10"], ["BP term", "GO:0050818", "regulation of coagulation", "8", "3.64E-10"], ["BP term", "GO:0032101", "regulation of response to external stimulus", "10", "3.43E-09"], ["BP term", "GO:0042060", "wound healing", "10", "1.43E-08"], ["BP term", "GO:0006953", "acute-phase response", "7", "1.91E-08"], ["BP term", "GO:0030195", "negative regulation of blood coagulation", "6", "8.61E-08"], ["BP term", "GO:0002526", "acute inflammatory response", "8", "7.76E-08"], ["BP term", "GO:0050817", "coagulation", "8", "9.16E-08"], ["BP term", "GO:0007596", "blood coagulation", "8", "9.16E-08"], ["BP term", "GO:0050819", "negative regulation of coagulation", "6", "1.17E-07"], ["BP term", "GO:0007599", "hemostasis", "8", "1.12E-07"], ["CC term", 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"section[12]/table-wrap[1]#T4", "version": null, "note": "The description of top 10 hub genes.", "structure": {"pmcid": "PMC7738106", "section_index": 12, "section_title": "Hub genes and analysis of hub genes", "row_count": 11, "column_count": 3}, "table": {"label": "Table 4", "caption": "The description of top 10 hub genes.", "rows": [["Gene symbol", "Gen description", "Degree"], ["FGA", "fibrinogen alpha chain", "29"], ["FGG", "fibrinogen gamma chain", "29"], ["ITIH2", "inter-alpha-trypsin inhibitor heavy chain 2", "29"], ["AHSG", "alpha 2-HS glycoprotein", "29"], ["APOA1", "apolipoprotein A1", "28"], ["APOB", "apolipoprotein B", "28"], ["F2", "coagulation factor II", "28"], ["APOA2", "apolipoprotein A2", "27"], ["PROC", "protein C", "27"], ["KNG1", "kininogen 1", "27"]], "row_count": 11, "column_count": 3, "numeric_cells": 13, "header_rows": 1, "locator": "section[12]/table-wrap[1]#T4"}}], "gaps": ["asset:data:geo:GSE15765 not downloaded", "asset:data:geo:GSE15765 licence not read", 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