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pmid:28302149
Identification and interaction analysis of key genes and microRNAs in hepatocellular carcinoma by bioinformatics analysis.
Tong Mou · Di Zhu · Xufu Wei · Tingting Li · Daofeng Zheng · Junliang Pu · Zhen Guo · Zhongjun Wu
World journal of surgical oncology · 2017 doi:10.1186/s12957-017-1127-2
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:28302149", "kind": "science-record", "revision": 7, "content_hash": "sha256:c9be403a1dabe772276a83182321e86b134b91c82a6177f4b24785f82286eee4", "created_at": "2026-11-01T15:40:24Z", "updated_at": "2026-11-01T21:59:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and interaction analysis of key genes and microRNAs in hepatocellular carcinoma by bioinformatics analysis.", "doi": "10.1186/s12957-017-1127-2", "pmid": "28302149", "authors": ["Tong Mou", "Di Zhu", "Xufu Wei", "Tingting Li", "Daofeng Zheng", "Junliang Pu", "Zhen Guo", "Zhongjun Wu"], "journal": "World journal of surgical oncology", "year": 2017, "abstract": "BACKGROUND: Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide. However, present studies of its multiple gene interaction and cellular pathways still could not explain the initiation and development of HCC perfectly. To find the key genes and miRNAs as well as their potential molecular mechanisms in HCC, microarray data GSE22058, GSE25097, and GSE57958 were analyzed.\nMETHODS: The microarray datasets GSE22058, GSE25097, and GSE57958, including mRNA and miRNA profiles, were downloaded from the GEO database and were analyzed using GEO2R. Functional and pathway enrichment analyses were performed using the DAVID database, and the protein-protein interaction (PPI) network was constructed using the Cytoscape software. Finally, miRDB was applied to predict the targets of the differentially expressed miRNAs (DEMs).\nRESULTS: A total of 115 differentially expressed genes (DEGs) were found in HCC, including 52 up-regulated genes and 63 down-regulated genes. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses from DAVID showed that up-regulated genes were significantly enriched in chromosome segregation and cell division, while the down-regulated genes were mainly involved in complement activation, protein activation cascades, carboxylic acid metabolic processes, oxoacid metabolic processes, and the immune response. From the PPI network, the 18 nodes with the highest degree were screened as hub genes. Among them, ESR1 was found to have close interactions with FOXO1, CXCL12, and GNAO1. In addition, a total of 64 DEMs were identified, which included 58 up-regulated miRNAs and 6 down-regulated miRNAs. ESR1 was potentially targeted by five miRNAs, including hsa-mir-18a and hsa-mir-221.\nCONCLUSIONS: The roles of DEMs like hsa-mir-221 in HCC through interactions with DEGs such as ESR1 and CXCL12 may provide new clues for the diagnosis and treatment of HCC patients.", "claims": [{"id": "claim-method", "statement": "The adjusted P values (adj. P) using Benjamini and Hochberg (BH) false discovery rate (FDR) method by default were applied to correct for the occurrence of false positive results. An adj. P < 0.05 and a |logFC| ≥ 1 were set as the cut-off criteria.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28302149", "locator": "sections[5] \"Data processing\" paragraph 2", "quote": "The adjusted P values (adj. P) using Benjamini and Hochberg (BH) false discovery rate (FDR) method by default were applied to correct for the occurrence of false positive results. An adj. P < 0.05 and a |logFC| ≥ 1 were set as the cut-off criteria."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets supporting the conclusions of this article are included within the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28302149", "locator": "sections[18] \"ack\" paragraph 1", "quote": "The datasets supporting the conclusions of this article are included within the article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study downloaded microarray datasets GSE22058, GSE25097, and GSE57958 from GEO and analyzed them with GEO2R using Benjamini–Hochberg-adjusted P values and a |logFC| ≥ 1 cutoff, identifying 115 DEGs and 64 DEMs in HCC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:28302149", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The microarray datasets GSE22058, GSE25097, and GSE57958, including mRNA and miRNA profiles, were downloaded from the GEO database and were analyzed using GEO2R."}, {"asset": "source:pmid:28302149", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 115 differentially expressed genes (DEGs) were found in HCC, including 52 up-regulated genes and 63 down-regulated genes."}, {"asset": "source:pmid:28302149", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In addition, a total of 64 DEMs were identified, which included 58 up-regulated miRNAs and 6 down-regulated miRNAs."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study downloaded microarray datasets GSE22058, GSE25097, and GSE57958 from GEO and analyzed them with GEO2R using Benjamini–Hochberg-adjusted P values and a |logFC| ≥ 1 cutoff, identifying 115 DEGs and 64 DEMs in HCC.", "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:28302149"], "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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"identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:28302149:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f08a04c6f659a3133433945734ead6b783daa8ea586d1cca566b56d2bc2cd418", "bytes": 741, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab2", "version": null, "note": "Hub genes and their related DEMs", "structure": {"pmcid": "PMC5356276", "section_index": 7, "section_title": "PPI network construction and analysis of modules", "row_count": 19, "column_count": 3}, "table": {"label": "Table 2", "caption": "Hub genes and their related DEMs", "rows": [["Gene symbol", "Node degree", "Related DEMs"], ["TOP2A", "30", "none"], ["FOS", "27", "hsa-miR-221"], ["TK1", "24", "none"], ["CDC20", "23", "none"], ["ESR1", "21", "hsa-miR-148b, hsa-miR-221, 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the genes in the module", "structure": {"pmcid": "PMC5356276", "section_index": 7, "section_title": "PPI network construction and analysis of modules", "row_count": 15, "column_count": 5}, "table": {"label": "Table 3", "caption": "Functional and pathway enrichment analysis of the genes in the module", "rows": [["Category", "Term", "Count", "%", "P Value"], ["GOTERM_BP_FAT", "GO:0000302 ~ response to reactive oxygen species", "4", "26.7", "8.25E-04"], ["GOTERM_BP_FAT", "GO:1901700 ~ response to oxygen-containing compound", "7", "46.7", "1.06E-03"], ["GOTERM_BP_FAT", "GO:0006979 ~ response to oxidative stress", "4", "26.7", "4.59E-03"], ["GOTERM_BP_FAT", "GO:0048545 ~ response to steroid hormone", "4", "26.7", "4.78E-03"], ["GOTERM_BP_FAT", "GO:1903047 ~ mitotic cell cycle process", "5", "33.3", "5.21E-03"], ["GOTERM_CC_FAT", "GO:0005654 ~ nucleoplasm", "9", "60.0", "1.54E-03"], ["GOTERM_CC_FAT", "GO:0005829 ~ cytosol", "8", "53.3", "1.94E-02"], ["GOTERM_CC_FAT", "GO:0005694 ~ chromosome", "4", "26.7", "4.75E-02"], ["GOTERM_MF_FAT", "GO:0044877 ~ macromolecular complex binding", "9", "60.0", "4.65E-06"], ["GOTERM_MF_FAT", "GO:0003682 ~ chromatin binding", "6", "40.0", "5.72E-05"], ["GOTERM_MF_FAT", "GO:0019899 ~ enzyme binding", "6", "40.0", "1.67E-02"], ["GOTERM_MF_FAT", "GO:0000982 ~ transcription factor activity, RNA polymer", "3", "20.0", "3.72E-02"], ["GOTERM_MF_FAT", "GO:0097367 ~ carbohydrate derivative binding", "6", "40.0", "4.13E-02"], ["KEGG_PATHWAY", "hsa04512:ECM-receptor interaction", "3", "20.0", "9.53E-03"]], "row_count": 15, "column_count": 5, "numeric_cells": 56, "header_rows": 1, "locator": "section[12]/table-wrap[2]#Tab3"}}, {"id": "asset:table:pmid:28302149:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:750de52125f3111231ee3af8d5d9c3ba96d95cdfab7808cc70ba5177ad1b25fe", "bytes": 2931, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#Tab1", "version": null, "note": "Functional and pathway enrichment analysis of up-regulated and down-regulated genes in hepatocellular carcinoma (HCC) tissue", "structure": {"pmcid": "PMC5356276", "section_index": 11, "section_title": "Functional and pathway enrichment analyses", "row_count": 34, "column_count": 5}, "table": {"label": "Table 1", "caption": "Functional and pathway enrichment analysis of up-regulated and down-regulated genes in hepatocellular carcinoma (HCC) tissue", "rows": [["Category", "Term", "Count", "%", "P Value"], ["Up-regulated"], ["GOTERM_BP_FAT", "GO:0007059 ~ chromosome segregation", "9", "17.6", "2.66E-06"], ["GOTERM_BP_FAT", "GO:0098813 ~ nuclear chromosome segregation", "8", "15.7", "1.06E-05"], ["GOTERM_BP_FAT", "GO:0000819 ~ sister chromatid segregation", "7", "13.7", "2.91E-05"], ["GOTERM_BP_FAT", "GO:0051301 ~ cell division", "9", "17.6", "1.31E-04"], ["GOTERM_BP_FAT", "GO:0007067 ~ mitotic nuclear division", "8", "15.7", "1.44E-04"], ["GOTERM_CC_FAT", "GO:0000793 ~ condensed chromosome", "5", "9.8", "2.14E-03"], ["GOTERM_CC_FAT", "GO:0005829 ~ cytosol", "18", "35.3", "3.98E-03"], ["GOTERM_CC_FAT", "GO:0005578 ~ proteinaceous extracellular matrix", "5", "9.8", "1.51E-02"], ["GOTERM_CC_FAT", "GO:0098651 ~ basement membrane collagen trimer", "2", "3.9", "2.08E-02"], ["GOTERM_CC_FAT", "GO:0005694 ~ chromosome", "7", "13.7", "3.38E-02"], ["GOTERM_MF_FAT", "GO:0042826 ~ histone deacetylase binding", "3", "5.9", "3.03E-02"], ["KEGG_PATHWAY", "hsa04512:ECM-receptor interaction", "3", "5.9", "1.68E-02"], ["Down-regulated"], ["GOTERM_BP_FAT", "GO:0006956 ~ complement activation", "6", "10.0", "1.83E-05"], ["GOTERM_BP_FAT", "GO:0072376 ~ protein activation cascade", "6", "10.0", "6.43E-05"], ["GOTERM_BP_FAT", "GO:0019752 ~ carboxylic acid metabolic process", "12", "20.0", "8.21E-05"], ["GOTERM_BP_FAT", "GO:0043436 ~ oxoacid metabolic process", "12", "20.0", "8.66E-05"], ["GOTERM_BP_FAT", "GO:0006955 ~ immune response", "16", "26.7", "1.23E-04"], ["GOTERM_CC_FAT", "GO:0005581 ~ collagen trimer", "4", "6.7", "7.15E-03"], ["GOTERM_CC_FAT", "GO:0072562 ~ blood microparticle", "4", "6.7", "1.91E-02"], ["GOTERM_CC_FAT", "GO:0005579 ~ membrane attack complex", "2", "3.3", "2.67E-02"], ["GOTERM_CC_FAT", "GO:0031988 ~ membrane-bounded vesicle", "21", "35.0", "4.60E-02"], ["GOTERM_CC_FAT", "GO:0044421 ~ extracellular region part", "22", "36.7", "5.00E-02"], ["GOTERM_MF_FAT", "GO:0005496 ~ steroid binding", "4", "6.7", "3.47E-03"], ["GOTERM_MF_FAT", "GO:0070330 ~ aromatase activity", "3", "5.0", "3.57E-03"], ["GOTERM_MF_FAT", "GO:0016712 ~ oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen", "3", "5.0", "4.11E-03"], ["GOTERM_MF_FAT", "GO:0004497 ~ monooxygenase activity", "4", "6.7", "4.77E-03"], ["GOTERM_MF_FAT", "GO:0004252 ~ serine-type endopeptidase activity", "5", "8.3", "7.38E-03"], ["KEGG_PATHWAY", "hsa05204:Chemical carcinogenesis", "6", "10.0", "4.53E-05"], ["KEGG_PATHWAY", "hsa00140:Steroid hormone biosynthesis", "4", "6.7", "3.04E-03"], ["KEGG_PATHWAY", "hsa00830:Retinol metabolism", "4", "6.7", "4.19E-03"], ["KEGG_PATHWAY", "hsa00982:Drug metabolism - cytochrome P450", "4", "6.7", "4.76E-03"]], "row_count": 34, "column_count": 5, "numeric_cells": 124, "header_rows": 1, "locator": "section[11]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:28302149:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f08a04c6f659a3133433945734ead6b783daa8ea586d1cca566b56d2bc2cd418", "bytes": 741, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab2", "version": null, "note": "Hub genes and their related DEMs", "structure": {"pmcid": "PMC5356276", "section_index": 12, "section_title": "PPI network construction and analysis of modules", "row_count": 19, "column_count": 3}, "table": {"label": "Table 2", "caption": "Hub genes and their related DEMs", "rows": [["Gene symbol", "Node degree", "Related DEMs"], ["TOP2A", "30", "none"], ["FOS", "27", "hsa-miR-221"], ["TK1", "24", "none"], ["CDC20", "23", "none"], ["ESR1", "21", "hsa-miR-148b, hsa-miR-221, hsa-miR-18a, hsa-miR-181b, hsa-miR-19a"], ["CCNB2", "18", "none"], ["CXCL12", "17", "hsa-miR-221"], ["FOXO1", "16", "hsa-miR-135b, hsa-miR-324-3p, hsa-miR-369-3p"], ["HMMR", "15", "none"], ["VWF", "15", "none"], ["ACSM3", "14", "none"], ["COL4A1", "14", "none"], ["ZIC2", "14", "none"], ["RFC4", "13", "none"], ["TXNRD1", "13", "none"], ["GNAO1", "12", "hsa-miR-193a"], ["CYP3A4", "10", "none"], ["RAP2A", "10", "none"]], "row_count": 19, "column_count": 3, "numeric_cells": 25, "header_rows": 1, "locator": "section[12]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:28302149:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a63f49009273bcd5628c31be2ab5c5b293fb770e11bb11e4562ca06a51589199", "bytes": 1381, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#Tab3", "version": null, "note": "Functional and pathway enrichment analysis of the genes in the module", "structure": {"pmcid": "PMC5356276", "section_index": 12, "section_title": "PPI network construction and analysis of modules", "row_count": 15, "column_count": 5}, "table": {"label": "Table 3", "caption": "Functional and pathway enrichment analysis of the genes in the module", "rows": [["Category", "Term", "Count", "%", "P Value"], ["GOTERM_BP_FAT", "GO:0000302 ~ response to reactive oxygen species", "4", "26.7", "8.25E-04"], ["GOTERM_BP_FAT", "GO:1901700 ~ response to oxygen-containing compound", "7", "46.7", "1.06E-03"], ["GOTERM_BP_FAT", "GO:0006979 ~ response to oxidative stress", "4", "26.7", "4.59E-03"], ["GOTERM_BP_FAT", "GO:0048545 ~ response to steroid hormone", "4", "26.7", "4.78E-03"], ["GOTERM_BP_FAT", "GO:1903047 ~ mitotic cell cycle process", "5", "33.3", "5.21E-03"], ["GOTERM_CC_FAT", "GO:0005654 ~ nucleoplasm", "9", "60.0", "1.54E-03"], ["GOTERM_CC_FAT", "GO:0005829 ~ cytosol", "8", "53.3", "1.94E-02"], ["GOTERM_CC_FAT", "GO:0005694 ~ chromosome", "4", "26.7", "4.75E-02"], ["GOTERM_MF_FAT", "GO:0044877 ~ macromolecular complex binding", "9", "60.0", "4.65E-06"], ["GOTERM_MF_FAT", "GO:0003682 ~ chromatin binding", "6", "40.0", "5.72E-05"], ["GOTERM_MF_FAT", "GO:0019899 ~ enzyme binding", "6", "40.0", "1.67E-02"], ["GOTERM_MF_FAT", "GO:0000982 ~ transcription factor activity, RNA polymer", "3", "20.0", "3.72E-02"], ["GOTERM_MF_FAT", "GO:0097367 ~ carbohydrate derivative binding", "6", "40.0", "4.13E-02"], ["KEGG_PATHWAY", "hsa04512:ECM-receptor interaction", "3", "20.0", "9.53E-03"]], "row_count": 15, "column_count": 5, "numeric_cells": 56, "header_rows": 1, "locator": "section[12]/table-wrap[2]#Tab3"}}, {"id": "asset:table:pmid:28302149:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c116d6514322d45ec9b4bcbfc0d6a087257714b60f0b133ff6a2730b0b81abff", "bytes": 1348, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#Tab4", "version": null, "note": "DEMs in HCC tissue and their potential target genes", "structure": {"pmcid": "PMC5356276", "section_index": 13, "section_title": "miRNA-DEG pairs", "row_count": 11, "column_count": 4}, "table": {"label": "Table 4", "caption": "DEMs in HCC tissue and their potential target genes", "rows": [["miRNA", "Adj. P", "logFC", "Target genes"], ["hsa-mir-106b", "1.94E-41", "1.49", "ANKRD29, IL1RAP, ADARB1, ARID4B, EPHA4, FBXL5, PDCD1LG2, PKD2, PTPN4, SLC40A1"], ["hsa-mir-148b", "9.59E-22", "1.37", "ESR1, ABCB7, B4GALT6, CDK19, LDLR, MXD1, NPTN, RPS6KA5, SOS2, SZRD1"], ["hsa-mir-151", "2.61E-21", "1.14", "AGO2, ZFAND5, CLK1, AQP4, CASD1, RPS6KA5, FAM104A, NAA15, YTHDF3, HIF1A"], ["hsa-mir-221", "7.37E-21", "1.66", "ESR1, FOS, CXCL12, CDKN1B, GABRA1, PANK3, TCF12, HECTD2, RFX7, TMCC1"], ["hsa-mir-18a", "2.16E-20", "2.48", "ESR1, NEDD9, BBX, INADL, MAP7D1, PHF19, RORA, ZBTB47, CDK19, DICER1"], ["hsa-mir-200b", "4.50E-17", "−3.15", "MAGEC2, ESM1, TCEB1, TRIM33, LHFP, PTPN21, ARHGAP6, VASH2, HIPK3, NR5A2"], ["hsa-mir-224", "4.85E-15", "−71.38", "NRCAM, CPNE8, ZNF207, ACSL4, RNF144B, SH3KBP1, RNF38, SLC4A4, GPR158, GGNBP2"], ["hsa-mir-200a", "5.03E-14", "−2.29", "COL15A1, MYBL1, ZEB2, ATP8A1, DCP2, TMEM170B, ZBTB34, DUSP3, TRHDE, RSAD2"], ["hsa-mir-182", "1.41E-06", "−2.69", "NRCAM, ABHD13, MFAP3, PCNX, NADK2, CAMSAP2, SLC39A9, NCALD, ANK3, HOXA9"], ["hsa-mir-142-5p", "6.59E-06", "−1.49", "ANKRD29, IGF2BP3, IGSF3, ZFP36, ZFPM2, BAI3, AFF4, DIAPH2, AHR, ARID4B"]], "row_count": 11, "column_count": 4, "numeric_cells": 40, "header_rows": 1, "locator": "section[13]/table-wrap[1]#Tab4"}}], "gaps": ["asset:data:geo:GSE22058 not downloaded", "asset:data:geo:GSE22058 licence not read", "asset:data:geo:GSE25097 not downloaded", "asset:data:geo:GSE25097 licence not read", "asset:data:geo:GSE57958 not downloaded", "asset:data:geo:GSE57958 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-2", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"id": "method-3", "family": null, "specific": null, "label": "Benjamini–Hochberg false discovery rate (FDR) adjustment using GEO2R", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The adjusted P values (adj. P) using Benjamini and Hochberg (BH) false discovery rate (FDR) method by default were applied to correct for the occurrence of false positive results. An adj. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE22058", "GSE25097", "GSE57958"], "resolved_accessions": ["GSE22058", "GSE25097", "GSE57958"], "statements": ["The datasets supporting the conclusions of this article are included within the article."], "basis": "The paper names GSE22058, GSE25097, GSE57958 in GEO database and the accession resolves in the repository. 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