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pmid:31987036
Integrated bioinformatics analysis for the screening of hub genes and therapeutic drugs in ovarian cancer.
Dan Yang · Yang He · Bo Wu · Yan Deng · Nan Wang · Menglin Li · Yang Liu
Journal of ovarian research · 2020 doi:10.1186/s13048-020-0613-2
Paper
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Experiment
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Data
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Analysis
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Complete file
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This study aims to identify hub genes and therapeutic drugs involved in OC.\nMETHODS: Four gene expression profiles (GSE54388, GSE69428, GSE36668, and GSE40595) were downloaded from the Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) in OC tissues and normal tissues with an adjusted P-value < 0.05 and a |log fold change (FC)| > 1.0 were first identified by GEO2R and FunRich software. Next, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses were performed for functional enrichment analysis of these DEGs. Then, the hub genes were identified by the cytoHubba plugin and the other bioinformatics approaches including protein-protein interaction (PPI) network analysis, module analysis, survival analysis, and miRNA-hub gene network construction was also performed. Finally, the GEPIA2 and DGIdb databases were utilized to verify the expression levels of hub genes and to select the candidate drugs for OC, respectively.\nRESULTS: A total of 171 DEGs were identified, including 114 upregulated and 57 downregulated DEGs. The results of the GO analysis indicated that the upregulated DEGs were mainly involved in cell division, nucleus, and protein binding, whereas the biological functions showing enrichment in the downregulated DEGs were mainly negative regulation of transcription from RNA polymerase II promoter, protein complex and apicolateral plasma membrane, and glycosaminoglycan binding. As for the KEGG-pathway, the upregulated DEGs were mainly associated with metabolic pathways, biosynthesis of antibiotics, biosynthesis of amino acids, cell cycle, and HTLV-I infection. Additionally, 10 hub genes (KIF4A, CDC20, CCNB2, TOP2A, RRM2, TYMS, KIF11, BIRC5, BUB1B, and FOXM1) were identified and survival analysis of these hub genes showed that OC patients with the high-expression of CCNB2, TYMS, KIF11, KIF4A, BIRC5, BUB1B, FOXM1, and CDC20 were statistically more likely to have poorer progression free survival. Meanwhile, the expression levels of the hub genes based on GEPIA2 were in accordance with those based on GEO. Finally, DGIdb database was used to identify 62 small molecules as the potentially targeted drugs for OC treatment.\nCONCLUSIONS: In summary, the data may produce new insights regarding OC pathogenesis and treatment. 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DTL, DSC2, DPP3, DHCR24, DGAT1, DDX39A, DBN1, CYC1, CTPS1, CRABP2, COPE, COL4A1, CLPTM1L, CLDN3, CHD7, CDH6, CDCA3, CDC20, CD47, CCNE1, CCNB2, C9orf16, C1orf106, BUB1B, BOLA2B, BIRC5, BAK1, AURKAIP1, ATP6V1B1, ASS1, ARL4C, ARF3, APOA1, AIF1L, ABHD11"], ["Downregulated (57)", "ZEB2, ZBTB20, WHAMMP2, WHAMMP3, WDR17, TLE4, THBD, TFPI, SYTL3, SNCAIP, SMIM14, SLC4A4, SCD5, RUNX1T1, RUNDC3B, RNASE4, PTPN13, PRKAR1A, PLCL2, PIP5K1B, PDK4, PDGFRA, NDNF, NBEA, N4BP2L2, N4BP2L1, MPDZ, MITF, MEF2C, MAF, FAM153A, FAM153B, FAM153C, KLHDC1, KLF2, KAT2B, KANSL1L, ITM2A, IL6ST, GPRASP1, GNG11, FOXP2, DPYD, DPY19L2P2, DMD, DCN, CXorf57, CIRBP, CHGB, CELF2, CDC14A, BNC2, ARMCX1, ALDH1A1, ABCA8, ABCA5, AASS"]], "row_count": 3, "column_count": 2, "numeric_cells": 4, "header_rows": 1, "locator": "section[11]/table-wrap[2]#Tab2"}}, {"id": "asset:table:pmid:31987036:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1e4e627789939a6491b78389d5f0b7425c94a66e31cf920f072c1dadbf138843", "bytes": 4888, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#Tab3", "version": null, "note": "Candidate drugs targeted by the hub genes", "structure": {"pmcid": "PMC6986075", "section_index": 16, "section_title": "Drug-gene interaction", "row_count": 63, "column_count": 6}, "table": {"label": "Table 3", "caption": "Candidate drugs targeted by the hub genes", "rows": [["No.", "Gene", "Drug", "Interaction types", "Sources", "PMIDs"], ["1", "TYMS", "ETOPOSIDE", "–", "PharmGKB", "–"], ["2", "TYMS", "IRINOTECAN", "–", "CIViC", "20,628,391"], ["3", "TYMS", "VINCRISTINE", "–", "NCI", "2,804,079"], ["4", "TYMS", "FOLIC ACID", "–", "PharmGKB", "–"], ["5", "TYMS", "TOPOTECAN", "–", "NCI", "10,803,925"], ["6", "TYMS", "CYTARABINE", "–", "PharmGKB", "–"], ["7", "TYMS", "MITOMYCIN", "–", "NCI", "15,218,314"], ["8", "TYMS", "PREDNISONE", "–", "PharmGKB", "–"], ["9", "TYMS", "TRIFLURIDINE", "inhibitor", "DrugBank", "18,600,528; 16,902,987; 20,372,850; 19,816,940; 19,886,911; 4,719,131; 6,436,227; 15,571,283; 17,179,993; 14,719,072; 16,010,590; 15,125,867; 11,752,352; 18,798,063; 6,010,427"], ["10", "TYMS", "DAUNORUBICIN", "–", "NCI", "2,967,076"], ["11", "TYMS", "HYDROCORTISONE", "–", "NCI", "2,707,640"], ["12", "TYMS", "PRALATREXATE", "inhibitor", "DrugBank", "23,409,799"], ["13", "TYMS", "PHENTOLAMINE", "–", "NCI", "2,866,100"], ["14", "TYMS", "TRIMETHOPRIM", "inhibitor", "DrugBank", "8,538,681; 10,090,784; 10,592,235; 17,139,284; 8,920,005; 17,016,423; 19,622,858"], ["15", "TYMS", "INDOMETHACIN", "–", "NCI", "2,707,640"], ["16", "TYMS", "GEMCITABINE", "inhibitor", "DrugBank", "16,563,096; 15,795,320; 17,166,391; 16,818,276; 11,752,352; 15,655,942; 16,818,496"], ["17", "TYMS", "ASPARAGINASE", "–", "PharmGKB", "–"], ["18", "TYMS", "CAPECITABINE", "inhibitor", "ClearityFoundationBiomarkers; ClearityFoundationClinicalTrial; GuideToPharmacologyInteractions; ChemblInteractions; DrugBank", "15,134,221; 16,926,630; 15,866,500; 15,132,128; 11,752,352; 15,709,193"], ["19", "TYMS", "FLOXURIDINE", "inhibitor", "TdgClinicalTrial; ClearityFoundationClinicalTrial; ChemblInteractions; TEND; DrugBank", "10,697,523; 10,891,536; 10,697,524; 10,482,907; 10,553,409"], ["20", "TYMS", "LEUCOVORIN", "–", "TdgClinicalTrial; TEND", "–"], ["21", "TYMS", "TAMOXIFEN", "–", "NCI", "9,615,734"], ["22", "TYMS", "VERAPAMIL", "–", "NCI", "3,436,366"], ["23", "TYMS", "RALTITREXED", "inhibitor", "PharmGKB; TdgClinicalTrial; GuideToPharmacologyInteractions; TEND; DrugBank", "18,773,878; 10,598,555; 10,430,100; 10,592,235; 11,752,352; 10,499,608; 10,482,907; 10,047,461; 10,496,350"], ["24", "TYMS", "PEMETREXED DISODIUM", "inhibitor", "ChemblInteractions", "–"], ["25", "TYMS", "DEXAMETHASONE", "–", "NCI", "2,707,640; 3,398,844"], ["26", "TYMS", "INTERFERON GAMA-1B", "–", "NCI", "1,557,656"], ["27", "TYMS", "FLUOROURACIL", "inhibitor", "ClearityFoundationClinicalTrial; ChemblInteractions; CIViC; DrugBank", "16,563,096; 20,628,391; 16,609,021; 16,719,540; 16,596,248; 16,538,493; 11,752,352; 15,353,299"], ["28", "TYMS", "OXALIPLATIN", "–", "PharmGKB", "–"], ["29", "TYMS", "TEGAFUR", "–", "TdgClinicalTrial", "–"], ["30", "TYMS", "SULFASALAZINE", "–", "PharmGKB", "–"], ["31", "TYMS", "PEMETREXED (CHEMBL1201258)", "inhibitor", "ClearityFoundationBiomarkers; TdgClinicalTrial; GuideToPharmacologyInteractions; CIViC; TEND", "23,645,741; 23,060,591; 21,367,480; 26,502,926"], ["32", "TYMS", "METHOTREXATE", "–", "CIViC", "23,652,803"], ["33", "BIRC5", "IRINOTECAN", "–", "NCI", "15,956,246"], ["34", "BIRC5", "INTERFERON BETA-1A", "–", "NCI", "12,117,359"], ["35", "BIRC5", "DOXORUBICIN", "–", "NCI", "16,211,302"], ["36", "BIRC5", "CYTARABINE", "–", "NCI", "14,713,572"], ["37", "BIRC5", "TRASTUZUMAB", "–", "NCI|CIViC", "16,452,223; 23,204,226"], ["38", "BIRC5", "LAPATINIB", "–", "NCI", "16,452,223"], ["39", "BIRC5", "PROXYPHYLLINE", "–", "NCI", "12,895,357"], ["40", "BIRC5", "PACLITAXEL", "–", "ClearityFoundationBiomarkers; NCI", "16,211,241; 15,347,474"], ["41", "BIRC5", "DOCETAXEL", "–", "ClearityFoundationBiomarkers", "–"], ["42", "BIRC5", "FLUTAMIDE", "–", "NCI", "15,735,703"], ["43", "BIRC5", "VORINOSTAT", "–", "NCI", "16,951,239"], ["44", "BIRC5", "PRASTERONE", "–", "NCI", "16,461,558"], ["45", "BIRC5", "ARSENIC TRIOXIDE", "–", "NCI", "15,587,394; 16,950,207"], ["46", "BIRC5", "ERLOTINIB", "–", "NCI", "17,047,074"], ["47", "BIRC5", "INDOMETHACIN", "–", "NCI", "17,270,149"], ["48", "BIRC5", "IMATINIB", "–", "NCI", "16,254,145"], ["49", "BIRC5", "ROMIDEPSIN", "–", "NCI", "14,767,553"], ["50", "BIRC5", "EPIRUBICIN", "–", "NCI", "16,608,080"], ["51", "BIRC5", "PLICAMYCIN", "–", "NCI", "17,124,180"], ["52", "BIRC5", "OMACETAXINE MEPESUCCINATE", "–", "NCI", "15,854,289"], ["53", "BIRC5", "MYCOPHENOLIC ACID", "–", "NCI", "15,571,295"], ["54", "BIRC5", "DEXAMETHASONE", "–", "NCI", "16,787,583"], ["55", "BIRC5", "FLUOROURACIL", "–", "NCI", "15,067,352"], ["56", "BIRC5", "DACTINOMYCIN", "–", "NCI", "15,883,285"], ["57", "BIRC5", "CALCITONIN", "–", "NCI", "16,222,118"], ["58", "BIRC5", "CARBOPLATIN", "–", "NCI", "15,347,474"], ["59", "BIRC5", "EPOETIN ALFA", "–", "NCI", "17,112,829"], ["60", "BIRC5", "TRETINOIN", "–", "NCI", "11,939,262; 14,587,026; 16,403,261"], ["61", "BIRC5", "METHOTREXATE", "–", "NCI", "15,670,151"], ["62", "BIRC5", "SULINDAC", "–", "NCI", "16,707,021; 16,950,207"]], "row_count": 63, "column_count": 6, "numeric_cells": 116, "header_rows": 1, "locator": "section[16]/table-wrap[1]#Tab3"}}], "gaps": ["asset:data:geo:GSE36668 not downloaded", "asset:data:geo:GSE36668 licence not read", "asset:data:geo:GSE40595 not downloaded", "asset:data:geo:GSE40595 licence not read", "asset:data:geo:GSE54388 not downloaded", "asset:data:geo:GSE54388 licence not read", "asset:data:geo:GSE69428 not downloaded", "asset:data:geo:GSE69428 licence not read"]}, "analysis": {"state": "complete", "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": 0.8, "band": "high", "quote": "GO enrichment"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", 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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": ["GSE54388", "GSE69428", "GSE36668", "GSE40595"], "resolved_accessions": ["GSE54388", "GSE69428", "GSE36668", "GSE40595"], "statements": ["The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request."], "basis": "The paper names GSE54388, GSE69428, GSE36668, GSE40595 in NCBI-GEO database and the accession resolves in the repository. 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