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pmid:32547947
Identification of Potential Key Genes for Pathogenesis and Prognosis in Prostate Cancer by Integrated Analysis of Gene Expression Profiles and the Cancer Genome Atlas.
Shuang Liu · Wenxin Wang · Yan Zhao · Kaige Liang · Yaojiang Huang
Frontiers in oncology · 2020 doi:10.3389/fonc.2020.00809
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Complete file
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There are still huge challenges in the treatment of prostate cancer. It is urgent to screen out potential key biomarkers for the pathogenesis and prognosis of PCa. Methods: Multiple gene differential expression profile datasets of PCa tissues and normal prostate tissues were integrated analysis by R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the overlapping Differentially Expressed Genes (DEG) were performed. The STRING online database was used in conjunction with Cytospace software for protein-protein interaction (PPI) network analysis to define hub genes. The relative mRNA expression of hub genes was detected in Gene Expression Profiling Interactive Analysis (GEPIA) database. A prognostic gene signature was identified by Univariate and multivariate Cox regression analysis. Results: Three hundred twelve up-regulated genes and 85 down-regulated genes were identified from three gene expression profiles (GSE69223, GSE3325, GSE55945) and The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset. Seven hub genes (FGF2, FLNA, FLNC, VCL, CAV1, ACTC1, and MYLK) further were detected, which related to the pathogenesis of PCa. Seven prognostic genes (BCO1, BAIAP2L2, C7, AP000844.2, ASB9, MKI67P1, and TMEM272) were screened to construct a prognostic gene signature, which shows good predictive power for survival by the ROC curve analysis. Conclusions: We identified a robust set of new potential key genes in PCa, which would provide reliable biomarkers for early diagnosis and prognosis and would promote molecular targeting therapy for PCa.", "claims": [{"id": "claim-method", "statement": "The DEGs of PCa and normal tissues were detected by limma package of R software (5), P-Val < 0.05 and absolute logFC > 1. 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"verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[3]#T3", "version": null, "note": "The overlapping downregulated DEGs between GSE69223, GSE3325, GSE55945, and TCGA PRAD dataset.", "structure": {"pmcid": "PMC7277826", "section_index": 10, "section_title": "Results", "row_count": 34, "column_count": 1}, "table": {"label": "Table 3", "caption": "The overlapping downregulated DEGs between GSE69223, GSE3325, GSE55945, and TCGA PRAD dataset.", "rows": [["Downregulated DEGs names"], ["TSLP,NUDT10,KCNJ3,FAT4,RAB40A,SBSPON,CCND2,GLIS3,ITIH5,RBMS3,"], ["KCNAB1,ATRNL1,HOXD13,SPOCK3,NRK,SLC8A1,TBX4,SPON1,JAZF1,SGCB,"], ["C1QTNF7,TWIST2,AFAP1L2,ANGPTL1,RNF180,HS3ST3A1,PLAC9,DAAM2,"], ["SNAI2,NELL2COL4A6,C2orf88,VCL,CFD,ME1,NHS,SEMA5A,AJUBA,OLFML1,"], ["CCDC8,PEG3,MAMDC2,ANGPT1,RBP4,FAM162B,C8orf88,RNF175,FBXO17,"], ["FERMT2,MAP1B,PLCL1,TRPC1,ANO5,TIMP3,PENK,ASPA,FXYD6,CLIC6,"], ["CCDC136,GSTM5,NT5E,C5orf34,EDNRB,PTGS1,LINGO2,PHYHIP,NDNF,FGF2,"], ["ZNF516,DKK3,CLIP4,BMP5,CCDC80,PCDH9,DCN,LPAR1,SLMAP,PRICKLE2,"], ["TPM2,MSRB3,SRD5A2,EID3,RNF112,ADAMTS5,ITGB1BP2,PALLD,CLU,"], ["GPM6B,MAMLD1,CAV2,LRRN3,TRIM6,PCDH10,ITGA1,RASL12,TSHZ3,"], ["DAB1,RND3,LGR6,EFEMP1,DUOXA1,LMOD1,TCEAL2,PTGIS,ZNF423,GSTM3,"], ["TCF7L1,ID4,FZD7,SCARA3,CAV1,SCN7A,SGCA,MYLK,TMEM200B,ACSS3,"], ["HCG11,RAB9B,SMOC1,RGS7BP,AHNAK2,TIMP4,ATP1A2,SLC2A5,DNAJB4,"], ["TSPAN18,S100A6,FBXL22,ST8SIA1,DZIP1,CDC42EP3,LINC01082,VWA5A,"], ["MLC1,RGS9,MXRA7,PTGER2,PNMA1,NDP,PLBD1,TGFBR3,TBX5,FHOD3,"], ["STARD4,FRMD6,PGM5,HLF,POPDC2,STAC,GSTM1,EFEMP2,MBNL1AS1,"], ["MYOCD,RBFOX3,FAM107A,CFL2,DNAJB5,BDNF,AOX1,ANO4,EPHA7,SLC14A1,"], ["RBPMS2,SYNC,SLC16A5,FLNA,DDR2,C3orf70,INMT,MRVI1,DOCK3,"], ["PPP1R14A,CCDC69,HSPB8,PPP1R1A,TMEM47,DPT,GPR87,TCEAL7,SGCG,"], ["SNX7,KLHL13,TRHDE,CYP3A5,GJA1,MAL,WFDC1,FLNC,B3GALT2,FOXF2,"], ["RRAS,CPNE5,MEIS1,CXCL13,PABPC4L,IGSF1,FILIP1L,MYOF,EPB41L3,"], ["GPRASP1,VIT,PDGFC,C2orf40,DSC3,C12orf75,EPHA2,GPX8,SLC24A3,"], ["CD200,C7,CRYAB,ZNF204P,SLC47A1,SCGB3A1,EPHB1,RCAN2,FHL1,ASB2,"], ["SLITRK6,CHRDL1,BCL11A,IL33,PRIMA1,GATA3,NEXN,SNHG18,PPP1R3C,"], ["LSAMP,UBXN10AS1,TMEM158,TENM2,PTGDS,FOXQ1,GPM6A,FOXF1,TGFB1I1,"], ["ACOX2,PARM1,HOXD10,RGN,KRT23,SYNDIG1,PGMAS1,WIF1,HSPB6,KCNJ8,"], ["HSPB3,EFS,PRTFDC1,SCGB1A1,AOC3,GSTP1,ZNF536,EDNRA,MIR100HG,"], ["SOWAHA,GSTM2,NSG1,MYH11,ROR2,SMR3B,NEURL1B,LINC00844,"], ["TMEM100,ID3,ACTC1,LAMB3,OGN,MYL9,LRCH2,IER3,SERPINF1,SYNPO2,"], ["DDIT4L,KIAA1210,PLN,PDZRN4,HSD11B1,IGDCC4,MEIS2,PYGM,PLA2G4A,"], ["DKK1,IP6K3,SMTNL2,SLC18A2,KRT14,CNN1,MYH6,JAKMIP1,CCK,ID1,"], ["KRT5,FLRT3,MME,SNX31,CYP4B1,LINC00261,MIR205HG,SLC39A2,UPK1A,"], ["BEX1,PTGS2,KRT13,TRG-AS1,TGM4,CD177,NEFH,SERPINB11"]], "row_count": 34, "column_count": 1, "numeric_cells": 30, "header_rows": 1, "locator": "section[10]/table-wrap[3]#T3"}}, {"id": "asset:table:pmid:32547947:5", "role": "table", "format": "jats-table", "media_type": 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"0.657(0.491–0.879)", "0.005", "0.999 (0.999–1.000)", "0.074", "−0.001"], ["AP000844.2", "1.743(1.2151–2.499)", "0.003", "1.004 (1.002–1.004)", "<0.001", "0.004"], ["ASB9", "1.828(1.315–2.541)", "<0.001", "1.002(1.002–1.006)", "0.039", "0.001"], ["MKI67P1", "5.033(1.977–12.804)", "0.001", "2.288(1.307–4.005)", "0.004", "0.828"], ["TMEM272", "2.545(1.479–4.380)", "0.001", "1.05(0.989–1.123)", "0.106", "0.053"]], "row_count": 9, "column_count": 6, "numeric_cells": 40, "header_rows": 2, "locator": "section[14]/table-wrap[1]#T4"}}], "gaps": ["asset:data:geo:GSE3325 not downloaded", "asset:data:geo:GSE3325 licence not read", "asset:data:geo:GSE55945 not downloaded", "asset:data:geo:GSE55945 licence not read", "asset:data:geo:GSE69223 not downloaded", "asset:data:geo:GSE69223 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "edger", "label": "Differential expression analysis", "dsl_operations": 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Using edgeR package of R software to normalize TCGA datasets and screen DEGs (6), P-Val < 0.05 and absolute logFC >1."}}, {"id": "method-2", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Cox regression"}}, {"id": "method-3", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-4", "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-5", "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"}}, {"id": "method-6", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.7, "band": "medium", "quote": "ROC curve"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: edger."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE69223", "GSE3325", "GSE55945"], "resolved_accessions": ["GSE69223", "GSE3325", "GSE55945"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: http://www.ncbi.nlm.nih.gov/geo/ and http://cancergenome.nih.gov/."], "basis": "The paper names GSE69223, GSE3325, GSE55945 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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