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pmid:34187556
Identification of hub genes associated with prognosis, diagnosis, immune infiltration and therapeutic drug in liver cancer by integrated analysis.
Xinyi Lei · Miao Zhang · Bingsheng Guan · Qiang Chen · Zhiyong Dong · Cunchuan Wang
Human genomics · 2021 doi:10.1186/s40246-021-00341-4
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Complete file
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The objective was to elucidate novel hub genes which were benefit for diagnosis, prognosis, and targeted therapy in liver cancer via integrated analysis.\nMETHODS: GSE84402, GSE101685, and GSE112791 were filtered from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified by using the GEO2R. The GO and KEGG pathway of DEGs were analyzed in the DAVID. PPI and TF network of the DEGs were constructed by using the STRING, TRANSFAC, and Harmonizome. The relationship between hub genes and prognoses in liver cancer was analyzed in UALCAN based on The Cancer Genome Atlas (TCGA). The diagnostic value of hub genes was evaluated by ROC. The relationship between hub genes and tumor-infiltrate lymphocytes was analyzed in TIMER. The protein levels of hub genes were verified in HPA. The interaction between the hub genes and the drug were identified in DGIdb.\nRESULTS: In total, 108 upregulated and 60 downregulated DEGs were enriched in 148 GO terms and 20 KEGG pathways. The mRNA levels and protein levels of CDK1, HMMR, PTTG1, and TTK were higher in liver cancer tissues compared to normal tissues, which showed excellent diagnostic and prognostic value. CDK1, HMMR, PTTG1, and TTK were positively correlated with tumor-infiltrate lymphocytes, which might involve tumor immune response. The CDK1, HMMR, and TTK had close interaction with anticancer agents.\nCONCLUSIONS: The CDK1, HMMR, PTTG1, and TTK were hub genes in liver cancer; hence, they might be potential biomarkers for diagnosis, prognosis, and targeted therapy of liver cancer.", "claims": [{"id": "claim-method", "statement": "The differentially expressed genes (DEGs) between liver cancer tissues and normal liver tissues of GSE84402, GSE101685, and GSE112791 were screened out by using GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r), respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34187556", "locator": "sections[5] \"Data processing\" paragraph 2", "quote": "The differentially expressed genes (DEGs) between liver cancer tissues and normal liver tissues of GSE84402, GSE101685, and GSE112791 were screened out by using GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r), respectively."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE84402 contained 14 liver cancer tissues and 14 matched corresponding non-cancerous liver tissues [14].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34187556", "locator": "sections[4] \"Data extraction\" paragraph 2", "quote": "The GSE84402 contained 14 liver cancer tissues and 14 matched corresponding non-cancerous liver tissues [14]."}], "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:34187556"], "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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["CD79A", "0.158", "**", "0.065", "0.212", "0.116", "*", "0.177", "***"], ["Monocyte", "CD86", "0.284", "***", "0.266", "***", "0.250", "***", "0.283", "***"], ["CD115", "0.131", "*", "0.138", "**", "0.102", "*", "0.119", "*"], ["TAM", "CCL2", "0.039", "0.459", "0.023", "0.656", "− 0.023", "0.665", "0.021", "0.682"], ["CD68", "0.230", "***", "0.186", "***", "0.149", "*", "0.204", "***"], ["IL10", "0.219", "***", "0.223", "***", "0.156", "*", "0.235", "***"], ["M1 macrophage", "NOS2", "− 0.020", "0.695", "0.080", "0.123", "− 0.140", "**", "− 0.005", "0.926"], ["IRF5", "0.394", "***", "0.407", "***", "0.291", "***", "0.373", "***"], ["COX2", "0.101", "0.053", "0.071", "0.171", "− 0.025", "0.637", "0.094", "0.070"], ["M2 Macrophage", "CD163", "0.067", "0.197", "0.153", "**", "− 0.022", "0.676", "0.073", "0.160"], ["VSIG4", "0.080", "0.123", "0.138", "**", "0.024", "0.647", "0.059", "0.255"], ["MS4A4A", "0.089", "0.086", "0.142", "**", "0.027", "0.601", "0.079", "0.128"], ["Neutrophils", 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"table": {"label": "Table 1", "caption": "DEGs in liver cancer samples compared with normal samples", "rows": [["DEGs", "Gene name"], ["Upregulated", "CCNB1, CDKN3, CCNB2, ASPM, TOP2A, UBE2T, BIRC5, FAM83D, MDK, KIF4A, CDK1, FAM72A///FAM72D///FAM72B///FAM72C, TTK, ANLN, CENPF, NCAPG, PBK, PTTG1, AURKA, RACGAP1, GPC3, NUF2, PRC1, GINS1, GMNN, RRM2, MELK, NEK2, CDC20, IQGAP3, NDC80, DLGAP5, ECT2, HMMR, KIF20A, SULT1C2, RAD51AP1, IGF2BP3, CENPK, DTL, DUXAP10, HELLS, FLVCR1, TYMS, CAP2, MAD2L1, UHRF1, KIAA0101, MCM6, PRR11, BUB1B, ACSL4, PEG10, CRNDE, ROBO1, SLC35F6///CENPA, CD24, CTHRC1, CKAP2, RBM24."], ["Downregulated", "CLEC4M, CLEC4G, OIT3, FCN3, CYP2A6, TTC36, FOSB, CYP1A2, APOF, FOS, FCN2, MT1G, GLS2, GBA3, LCAT, CLEC1B, KCNN2, CXCL14, GLYAT, HGF, MARCO, CYP39A1, MT1X, GPM6A, HHIP, ANXA10, C8A, MT1M, TMEM27, GYS2, AKR1D1, HAMP, MT1F, PLAC8, CYP2B6, C7, KMO, MT1H, NAT2, SLC22A1, CYP2A7, CNDP1, MT1HL1, C3P1, BCO2, CRHBP, MT1E, GSTZ1, KCND3, SORL1, HAO2, ADH1B, CYP4A11, EGR1, ESR1, SLC25A47, CYP4A22///CYP4A11, GNMT, HGFAC, LINC01093, F9, SRPX, LINC00844, HEPN1///HEPACAM, SRD5A2, CYP2B7P///CYP2B6, MFSD2A, FLJ22763, FOLH1, BBOX1, SDS, BCHE, C9, SLC10A1, TSLP, LYVE1, MME, PGLYRP2, DCN, CYP3A4, CYP8B1, KBTBD11, GHR, CTH, CFHR4, AADAT, CXCL2, CYP26A1, C6, CETP, PDGFRA, FBP1, SERPINE1, RSPO3, PBLD, RDH16, SLCO1B3, IDO2, PZP, LPA, PCK1, AFM, ASPA, CLRN3, CNTN3, HPGD, ACSM3, LOC101928916///NNMT."]], "row_count": 3, "column_count": 2, "numeric_cells": 2, "header_rows": 1, "locator": "section[14]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:34187556:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:70167caa29f8753bd776ce0b6c621e119f330255d35a6fa2c98cbab9c564de16", "bytes": 2795, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#Tab2", "version": null, "note": "The topology properties of 41 hub genes (The genes are ranked by degree)", "structure": {"pmcid": "PMC8243535", "section_index": 16, "section_title": "PPI network and significant module analysis in liver cancer", "row_count": 42, "column_count": 7}, "table": {"label": "Table 2", "caption": "The topology properties of 41 hub genes (The genes are ranked by degree)", "rows": [["Genes", "Degree", "Betweenness centrality", "Closeness centrality", "Clustering coefficient", "Stress", "Average shortest path length"], ["CDC20", "41", "4.09E-02", "9.36E-01", "7.48E-01", "446", "1.07"], ["CDK1", "40", "2.89E-02", "9.17E-01", "7.79E-01", "398", "1.09"], ["TOP2A", "40", "3.73E-02", "9.17E-01", "7.67E-01", "394", "1.09"], ["BUB1B", "39", "1.65E-02", "8.98E-01", "7.99E-01", "320", "1.11"], ["CCNB2", "39", "1.06E-02", "8.98E-01", "8.19E-01", "284", "1.11"], ["NCAPG", "39", "2.64E-02", "8.98E-01", "7.96E-01", "354", "1.11"], ["ASPM", "39", "1.50E-02", "8.98E-01", "8.08E-01", "302", "1.11"], ["AURKA", "38", "8.26E-03", "8.80E-01", "8.45E-01", "232", 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"column_count": 10}, "table": {"label": "Table 3", "caption": "Correlation analysis between CDK1, HMMR, PTTG1, and TTK and related immune markers in immune cells, as evaluated using TIMER", "rows": [["Description", "Gene marker", "CDK1", "HMMR", "PTTG1", "TTK"], ["Cor", "P", "Cor", "P", "Cor", "P", "Cor", "P"], ["CD8+ T cell", "CD8A", "0.198", "***", "0.139", "**", "0.164", "**", "0.188", "***"], ["CD8B", "0.184", "***", "0.096", "0.064", "0.226", "***", "0.165", "**"], ["T cell (general)", "CD3D", "0.274", "***", "0.154", "**", "0.333", "***", "0.266", "***"], ["CD3E", "0.202", "***", "0.120", "*", "0.175", "***", "0.195", "***"], ["CD2", "0.216", "***", "0.121", "*", "0.204", "***", "0.204", "***"], ["B cell", "CD19", "0.273", "***", "0.204", "***", "0.247", "***", "0.273", "***"], ["CD79A", "0.158", "**", "0.065", "0.212", "0.116", "*", "0.177", "***"], ["Monocyte", "CD86", "0.284", "***", "0.266", "***", "0.250", "***", "0.283", "***"], ["CD115", "0.131", "*", "0.138", "**", 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"data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The differentially expressed genes (DEGs) between liver cancer tissues and normal liver tissues of GSE84402, GSE101685, and GSE112791 were screened out by using GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r), respectively."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", 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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": ["GSE84402", "GSE101685", "GSE112791"], "resolved_accessions": ["GSE84402", "GSE101685", "GSE112791"], "statements": ["The GSE84402 contained 14 liver cancer tissues and 14 matched corresponding non-cancerous liver tissues [14]."], "basis": "The paper names GSE84402, GSE101685, GSE112791 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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