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pmid:25551447
Meta-analysis of prostate cancer gene expression data identifies a novel discriminatory signature enriched for glycosylating enzymes.
Stefan J Barfeld · Philip East · Verena Zuber · Ian G Mills
BMC medical genomics · 2014 doi:10.1186/s12920-014-0074-9
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Prostate cancer is, however, a heterogeneous multifocal cancer and this poses challenges in identifying robust transcript biomarkers.\nMETHODS: In this study, we have undertaken a meta-analysis of publicly available transcriptomic data spanning datasets and technologies from the last decade and encompassing laser capture microdissected and macrodissected sample sets.\nRESULTS: We identified a 33 gene signature that can discriminate between benign tissue controls and localised prostate cancers irrespective of detection platform or dissection status. These genes were significantly overexpressed in localised prostate cancer versus benign tissue in at least three datasets within the Oncomine Compendium of Expression Array Data. In addition, they were also overexpressed in a recent exon-array dataset as well a prostate cancer RNA-seq dataset generated as part of the The Cancer Genomics Atlas (TCGA) initiative. Biologically, glycosylation was the single enriched process associated with this 33 gene signature, encompassing four glycosylating enzymes. We went on to evaluate the performance of this signature against three individual markers of prostate cancer, v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) expression, prostate specific antigen (PSA) expression and androgen receptor (AR) expression in an additional independent dataset. Our signature had greater discriminatory power than these markers both for localised cancer and metastatic disease relative to benign tissue, or in the case of metastasis, also localised prostate cancer.\nCONCLUSION: In conclusion, robust transcript biomarkers are present within datasets assembled over many years and cohorts and our study provides both examples and a strategy for refining and comparing datasets to obtain additional markers as more data are generated.", "claims": [{"id": "claim-method", "statement": "To determine if any of the enriched modules were capable of segregating samples on phenotype we built contingency tables across clinical conditions from each of the data sets (Tomlins [5] and Ramaswamy [6]) for induced and repressed modules and tested for sample enrichment using a Fisher’s Exact test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:25551447", "locator": "sections[7] \"Phenotype segregation\" paragraph 2", "quote": "To determine if any of the enriched modules were capable of segregating samples on phenotype we built contingency tables across clinical conditions from each of the data sets (Tomlins [5] and Ramaswamy [6]) for induced and repressed modules and tested for sample enrichment using a Fisher’s Exact test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The expression array data were downloaded from GEO under accession number GSE3325 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE3325).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:25551447", "locator": "sections[3] \"Description of datasets\" paragraph 2", "quote": "The expression array data were downloaded from GEO under accession number GSE3325 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE3325)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A meta-analysis using public transcriptomic data from multiple datasets, detection platforms, and dissection methods identified a 33-gene signature that discriminated benign tissue from localised prostate cancer.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:25551447", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified a 33 gene signature that can discriminate between benign tissue controls and localised prostate cancers irrespective of detection platform or dissection status."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A meta-analysis using public transcriptomic data from multiple datasets, detection platforms, and dissection methods identified a 33-gene signature that discriminated benign tissue from localised prostate cancer.", "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:25551447"], "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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"resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:25551447:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2cb5ede2e698480a688ed010a1d88effce921fbb4820299e78b38d607f36e512", "bytes": 8143, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#Tab1", "version": null, "note": "KEGG pathway enrichment analysis for the genes comprising signature 1 (101.6.1)", "structure": {"pmcid": "PMC4351903", "section_index": 13, "section_title": "Results and discussion", "row_count": 36, "column_count": 13}, "table": {"label": "Table 1", "caption": "KEGG pathway enrichment analysis for the genes comprising signature 1 (101.6.1)", "rows": [["Category", "Term", "Count", "%", "PValue", "Genes", "List Total", "Pop Hits", "Pop Total", "Fold Enrichment", 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ITPR1, ITPR2, EDNRA, AGTR1, EDNRB, GNAL, CD38, PLCB4, GNAQ, CHRM3, PLN, CAMK2D, PPP3CB, PRKACB, PLCB1, MYLK", "404", "176", "5085", "1.5", "1", "0.37", "54.64"], ["KEGG_PATHWAY", "hsa04530:Tight junction", "17", "1.31", "0.06", "PRKCA, ACTB, RAB3B, MYL5, MAGI2, ZAK, MYL2, MPDZ, GNAI1, ACTN1, AMOTL1, PTEN, MYL9, EPB41L2, MYH11, RRAS, JAM2, PTENP1", "404", "134", "5085", "1.6", "1", "0.36", "54.73"], ["KEGG_PATHWAY", "hsa05222:Small cell lung cancer", "12", "0.93", "0.07", "COL4A4, PTGS2, CDK6, RB1, PTEN, COL4A6, LAMB3, LAMA4, LAMB2, ITGA6, PIAS1, MYC, PTENP1", "404", "84", "5085", "1.8", "1", "0.36", "56.55"], ["KEGG_PATHWAY", "hsa04360:Axon guidance", "16", "1.24", "0.08", "LIMK2, GNAI1, MET, NTN4, SLIT2, EPHA3, SEMA5A, EPHA4, EPHB6, CFL2, PPP3CB, SEMA3C, EFNA5, UNC5D, PAK1, RASA1", "404", "129", "5085", "1.56", "1", "0.42", "65.75"], ["KEGG_PATHWAY", "hsa04115:p53 signaling pathway", "10", "0.77", "0.09", "SERPINB5, CCND2, SERPINE1, IGF1, CDK6, FAS, GADD45B, THBS1, CCNG2, PTEN, 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discussion", "row_count": 4, "column_count": 13}, "table": {"label": "Table 6", "caption": "KEGG pathway enrichment analysis for the entire set of overexpressed genes in localised prostate cancer versus benign tissue in the Varambally dataset (GSE3325)", "rows": [["Category", "Term", "Count", "%", "PValue", "Genes", "List Total", "Pop Hits", "Pop Total", "Fold Enrichment", "Bonferroni", "Benjamini", "FDR"], ["KEGG_PATHWAY", "hsa00512:O-Glycan biosynthesis", "3", "0.34", "0.01", "GALNTL4, GCNT1, ST6GALNAC1", "26", "30", "5085", "19.56", "0.43", "0.43", "8.95"], ["KEGG_PATHWAY", "hsa04610:Complement and coagulation cascades", "3", "0.34", "0.04", "C4A, C4B, SERPINA1", "26", "69", "5085", "8.5", "0.94", "0.75", "36.76"], ["KEGG_PATHWAY", "hsa05322:Systemic lupus erythematosus", "3", "0.34", "0.08", "C4A, C4B, HLA-DMB", "26", "99", "5085", "5.93", "1", "0.83", "58.75"]], "row_count": 4, "column_count": 13, "numeric_cells": 33, "header_rows": 1, "locator": 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