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Meta-analysis of prostate cancer gene expression data identifies a novel discriminatory signature enriched for glycosylating enzymes

BACKGROUND: Tumorigenesis is characterised by changes in transcriptional control. Extensive transcript expression data have been acquired over the last decade and used to classify prostate cancers. Prostate cancer is, however, a heterogeneous multifocal cancer and this poses challenges in identifyin...

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Autores principales: Barfeld, Stefan J, East, Philip, Zuber, Verena, Mills, Ian G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351903/
https://www.ncbi.nlm.nih.gov/pubmed/25551447
http://dx.doi.org/10.1186/s12920-014-0074-9
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author Barfeld, Stefan J
East, Philip
Zuber, Verena
Mills, Ian G
author_facet Barfeld, Stefan J
East, Philip
Zuber, Verena
Mills, Ian G
author_sort Barfeld, Stefan J
collection PubMed
description BACKGROUND: Tumorigenesis is characterised by changes in transcriptional control. Extensive transcript expression data have been acquired over the last decade and used to classify prostate cancers. Prostate cancer is, however, a heterogeneous multifocal cancer and this poses challenges in identifying robust transcript biomarkers. METHODS: 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. RESULTS: 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. CONCLUSION: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-014-0074-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-43519032015-03-07 Meta-analysis of prostate cancer gene expression data identifies a novel discriminatory signature enriched for glycosylating enzymes Barfeld, Stefan J East, Philip Zuber, Verena Mills, Ian G BMC Med Genomics Research Article BACKGROUND: Tumorigenesis is characterised by changes in transcriptional control. Extensive transcript expression data have been acquired over the last decade and used to classify prostate cancers. Prostate cancer is, however, a heterogeneous multifocal cancer and this poses challenges in identifying robust transcript biomarkers. METHODS: 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. RESULTS: 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. CONCLUSION: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-014-0074-9) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-31 /pmc/articles/PMC4351903/ /pubmed/25551447 http://dx.doi.org/10.1186/s12920-014-0074-9 Text en © Barfeld et al.; licensee BioMed Central. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Barfeld, Stefan J
East, Philip
Zuber, Verena
Mills, Ian G
Meta-analysis of prostate cancer gene expression data identifies a novel discriminatory signature enriched for glycosylating enzymes
title Meta-analysis of prostate cancer gene expression data identifies a novel discriminatory signature enriched for glycosylating enzymes
title_full Meta-analysis of prostate cancer gene expression data identifies a novel discriminatory signature enriched for glycosylating enzymes
title_fullStr Meta-analysis of prostate cancer gene expression data identifies a novel discriminatory signature enriched for glycosylating enzymes
title_full_unstemmed Meta-analysis of prostate cancer gene expression data identifies a novel discriminatory signature enriched for glycosylating enzymes
title_short Meta-analysis of prostate cancer gene expression data identifies a novel discriminatory signature enriched for glycosylating enzymes
title_sort meta-analysis of prostate cancer gene expression data identifies a novel discriminatory signature enriched for glycosylating enzymes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351903/
https://www.ncbi.nlm.nih.gov/pubmed/25551447
http://dx.doi.org/10.1186/s12920-014-0074-9
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