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pmid:31010415
Identification of significant genes with poor prognosis in ovarian cancer via bioinformatical analysis.
Hao Feng · Zhong-Yi Gu · Qin Li · Qiong-Hua Liu · Xiao-Yu Yang · Jun-Jie Zhang
Journal of ovarian research · 2019 doi:10.1186/s13048-019-0508-2
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Complete file
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The purpose of the present academic work was to identify significant genes with poor outcome and their underlying mechanisms. Gene expression profiles of GSE36668, GSE14407 and GSE18520 were available from GEO database. There are 69 OC tissues and 26 normal tissues in the three profile datasets. Differentially expressed genes (DEGs) between OC tissues and normal ovarian (OV) tissues were picked out by GEO2R tool and Venn diagram software. Next, we made use of the Database for Annotation, Visualization and Integrated Discovery (DAVID) to analyze Kyoto Encyclopedia of Gene and Genome (KEGG) pathway and gene ontology (GO). Then protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). There were total of 216 consistently expressed genes in the three datasets, including 110 up-regulated genes enriched in cell division, sister chromatid cohesion, mitotic nuclear division, regulation of cell cycle, protein localization to kinetochore, cell proliferation and Cell cycle, progesterone-mediated oocyte maturation and p53 signaling pathway, while 106 down-regulated genes enriched in palate development, blood coagulation, positive regulation of transcription from RNA polymerase II promoter, axonogenesis, receptor internalization, negative regulation of transcription from RNA polymerase II promoter and no significant signaling pathways. Of PPI network analyzed by Molecular Complex Detection (MCODE) plug-in, all 33 up-regulated genes were selected. Furthermore, for the analysis of overall survival among those genes, Kaplan-Meier analysis was implemented and 20 of 33 genes had a significantly worse prognosis. For validation in Gene Expression Profiling Interactive Analysis (GEPIA), 15 of 20 genes were discovered highly expressed in OC tissues compared to normal OV tissues. Furthermore, four genes (BUB1B, BUB1, TTK and CCNB1) were found to significantly enrich in the cell cycle pathway via re-analysis of DAVID. In conclusion, we have identified four significant up-regulated DEGs with poor prognosis in OC on the basis of integrated bioinformatical methods, which could be potential therapeutic targets for OC patients.", "claims": [{"id": "claim-method", "statement": "The log rank P value and hazard ratio (HR) with 95% confidence intervals were computed and showed on the plot.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31010415", "locator": "sections[7] \"Survival analysis and RNA sequencing expression of core genes\" paragraph 2", "quote": "The log rank P value and hazard ratio (HR) with 95% confidence intervals were computed and showed on the plot."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed in the present study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31010415", "locator": "sections[18] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analyzed in the present study are available from the corresponding author on reasonable request."}], "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:31010415"], "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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RRM2 SLC35F6///CENPA TOP2A WDR72 S100A2 PAX8 KIF15 WFDC2 TFAP2A BUB1B TIMELESS NR2F6 MECOM RAD51AP1 ESCO2 LYNX1 ESRP1 DTL FAM83D HMMR C12orf56 GPM6B LOC101928554 CENPK LCN2 PRAME KIAA0101 HMGA1 TTK NCAPG CP SLC52A2 LINC01296///DUXAP10 NEK2 CENPF NUSAP1 ST6GALNAC1"], ["Down-regulated", "MUM1L1 NAP1L2 CYP2U1 VGLL3 GHR NEFH TMEM255A PPM1K TSPAN8 BAMBI MICU3 OC101930363///LOC101928349///LOC100507387///FAM153C///FAM153A///FAM153B LOC100507387///FAM153A///FAM153B BDH2 DPYD ANTXR2 HLF PRSS35 THBD PRRX1 LY75-CD302///CD302///LY75 ABCA8 WDR17 ZFPM2 OMD TCF21 PDGFD KLF2 SNCAIP NEGR1 NT5E RUNX1T1 TRPC1 SNCA PLEKHH2 GAS1RR MTUS1 GPM6A CPED1 MGARP LSAMP EFEMP1 B3GALT2 CHGB DIRAS3 PRKAR2B FAM13C KCNT2 TMEM150C ECM2 GIPC2 OGN SNX29P2 ARX TCEAL2 NAP1L3 SDPR TCEAL7 NBEA CXorf57 CSGALNACT1 CYS1 CNTN1 AKAP12 MEOX2 COL14A1 CALCRL ALDH1A1 SMPD3 TBX3 WNT2B ANKRD29 NR2F1-AS1 MCC CBLN4 CELF2 ITM2A GNG11 PGR OGFOD1 TFPI GPRASP1 PEG3 PCDH9 HAND2-AS1 RBMS3 FGF13 PRDM5 MAF PDE8B SIGLEC11 TLE4 DCN PEX5L BNC2 GATM RNF128 LHX9 AOX1 AKT3 OLFML1 RNASE4 GATA4 NXPH2 NDN LOC100506718///FLRT2"]], "row_count": 3, "column_count": 2, "numeric_cells": 2, "header_rows": 1, "locator": "section[9]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:31010415:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9e019f79efdda720ae65348059b9707ccd5e1f1e14f498c46957883234b9a0c4", "bytes": 3481, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#Tab2", "version": null, "note": "Gene ontology analysis of differentially expressed genes in ovarian cancer", "structure": {"pmcid": "PMC6477749", "section_index": 10, "section_title": "DEGs gene ontology and KEGG pathway analysis in ovarian cancers", "row_count": 33, "column_count": 7}, "table": {"label": "Table 2", "caption": "Gene ontology analysis of differentially expressed genes in ovarian cancer", "rows": [["Expression", "Category", "Term", "Count", "%", "p-Value", "FDR"], ["Up-regulated", "GOTERM_BP_DIRECT", "GO:0051301~cell division", "16", "15.24", "9.45E-10", "1.43E-06"], ["GOTERM_BP_DIRECT", "GO:0007067~mitotic nuclear division", "14", "13.33", "1.21E-09", "1.84E-06"], ["GOTERM_BP_DIRECT", "GO:0007062~sister chromatid cohesion", "8", "7.62", "1.76E-06", "0.002667"], ["GOTERM_BP_DIRECT", "GO:0051726~regulation of cell cycle", "8", "7.62", "6.07E-06", "0.009214"], ["GOTERM_BP_DIRECT", "GO:0034501~protein localization to kinetochore", "4", "3.81", "1.98E-05", "0.030061"], ["GOTERM_BP_DIRECT", "GO:0008283~cell proliferation", "11", "10.48", "3.81E-05", "0.057753"], ["GOTERM_CC_DIRECT", "GO:0005654~nucleoplasm", "37", "35.24", "8.26E-08", "9.94E-05"], ["GOTERM_CC_DIRECT", "GO:0030496~midbody", "9", "8.57", "3.99E-07", "4.80E-04"], ["GOTERM_CC_DIRECT", "GO:0005876~spindle microtubule", "6", "5.71", "3.37E-06", "0.004057"], ["GOTERM_CC_DIRECT", "GO:0005819~spindle", "8", "7.62", "3.49E-06", "0.004203"], ["GOTERM_CC_DIRECT", "GO:0005829~cytosol", "35", "33.33", "4.42E-05", "0.053183"], ["GOTERM_CC_DIRECT", "GO:0005634~nucleus", "48", "45.71", "5.52E-05", "0.066432"], ["GOTERM_MF_DIRECT", "GO:0005515~protein binding", "72", "68.57", "5.60E-07", "7.08E-04"], ["GOTERM_MF_DIRECT", "GO:0043565~sequence-specific DNA binding", "11", "10.48", "5.14E-04", "0.647343"], ["GOTERM_MF_DIRECT", "GO:0008017~microtubule binding", "7", "6.67", "9.63E-04", "1.210835"], ["GOTERM_MF_DIRECT", "GO:0008574~ATP-dependent microt-ubule motor activity, plus-end-directed", "3", "2.86", "0.003788", "4.685832"], ["GOTERM_MF_DIRECT", "GO:0019901~protein kinase binding", "8", "7.62", "0.0044544", "5.488301"], ["Down-regulated", "GOTERM_BP_DIRECT", "GO:0060021~palate development", "5", "4.91", "4.95E-04", "0.721802"], ["GOTERM_BP_DIRECT", "GO:0007596~blood coagulation", "6", "5.89", "0.001956", "2.823695"], ["GOTERM_BP_DIRECT", "GO:0045944~positive regulation of transcription from RNA polymerase II promoter", "12", "11.76", "0.00728", "10.1353"], ["GOTERM_BP_DIRECT", "GO:0000122~negative regulation of transcription from RNA polymerase II promoter", "10", "9.80", "0.00773", "10.72979"], ["GOTERM_BP_DIRECT", "GO:0007409~axonogenesis", "4", "3.92", "0.011841", "15.98884"], ["GOTERM_BP_DIRECT", "GO:0031623~receptor internalization", "3", "2.94", "0.018262", "23.62882"], ["GOTERM_CC_DIRECT", "GO:0031225~anchored component of membrane", "5", "4.90", "0.002893", "3.225113"], ["GOTERM_CC_DIRECT", "GO:0005576~extracellular region", "17", "16.67", "0.008777", "9.4952"], ["GOTERM_CC_DIRECT", "GO:0005578~proteinaceous extracellular matrix", "6", "5.88", "0.013131", "13.89424"], ["GOTERM_CC_DIRECT", "GO:0005615~extracellular space", "14", "13.72", "0.022365", "22.58432"], ["GOTERM_MF_DIRECT", "GO:0043565~sequence-specific DNA binding", "10", "9.80", "0.00117", "1.454993"], ["GOTERM_MF_DIRECT", "GO:0001078~transcriptional repressor activity, RNA polymerase II core promoter 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"application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2aca246bb7a4d0850826f860ef58e00b31b270835231d55acc065fb312983249", "bytes": 542, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab4", "version": null, "note": "The prognostic information of the 33 key candidate genes", "structure": {"pmcid": "PMC6477749", "section_index": 12, "section_title": "Analysis of core genes by the Kaplan Meier plotter and GEPIA", "row_count": 3, "column_count": 2}, "table": {"label": "Table 4", "caption": "The prognostic information of the 33 key candidate genes", "rows": [["Category", "Genes"], ["Genes with significantly worse survival (P < 0.05)", "BUB1 BUB1B CCNB1 CDCA5 CENPF CENPK DEPDC1 ECT2 FAM83D FOXM1 HMMR KIF11 KIF14 KIF15 MCM10 NCAPG RAD51AP1 TIMELESS TTK UBE2C"], ["Genes without significantly worse survival (P > 0.05)", "AURKB CCNB2 CDC20 DTL E2F1 KIAA0101 KIF4A MELK NEK2 NUSAP1 PRC1 RRM2 TRIP13"]], "row_count": 3, "column_count": 2, "numeric_cells": 4, "header_rows": 1, "locator": "section[12]/table-wrap[1]#Tab4"}}, {"id": "asset:table:pmid:31010415:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:99b2bc0c0e5f4f0ad1cb55e97bb5eed40eefc4167aeb628182b06cec4750c50f", "bytes": 426, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#Tab5", "version": null, "note": "Vadidation of 20 genes via GEPIA", "structure": {"pmcid": "PMC6477749", "section_index": 12, "section_title": "Analysis of core genes by the Kaplan Meier plotter and GEPIA", "row_count": 3, "column_count": 2}, "table": {"label": "Table 5", "caption": "Vadidation of 20 genes via GEPIA", "rows": [["Category", "Genes"], ["Genes with high expressed in OC (P < 0.05)", "BUB1 BUB1B CCNB1 CDCA5 CENPF DEPDC1 ECT2 FAM83D FOXM1 HMMR KIF11 NCAPG RAD51AP1 TTK UBE2C"], ["Genes without high expressed in OC (P > 0.05)", "CENPK KIF14 KIF15 MCM10 TIMELESS"]], "row_count": 3, "column_count": 2, "numeric_cells": 4, "header_rows": 1, "locator": "section[12]/table-wrap[2]#Tab5"}}, {"id": "asset:table:pmid:31010415:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e10906ff5c84e5a98109bcb892becd6d8426eabd270988f7ffcf8b9b47702076", "bytes": 420, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#Tab6", "version": null, "note": "Re-analysis of 15 selected genes via KEGG pathway enrichment", "structure": {"pmcid": "PMC6477749", "section_index": 13, "section_title": "Re-analysis of 15 selected genes via KEGG pathway enrichment", "row_count": 3, "column_count": 6}, "table": {"label": "Table 6", "caption": "Re-analysis of 15 selected genes via KEGG pathway enrichment", "rows": [["Pathway ID", "Name", "Count", 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