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dc.contributor.authorHaider, S
dc.contributor.authorWang, J
dc.contributor.authorNagano, A
dc.contributor.authorDesai, A
dc.contributor.authorArumugam, P
dc.contributor.authorDumartin, L
dc.contributor.authorFitzgibbon, J
dc.contributor.authorHagemann, T
dc.contributor.authorMarshall, JF
dc.contributor.authorKocher, HM
dc.contributor.authorCrnogorac-Jurcevic, T
dc.contributor.authorScarpa, A
dc.contributor.authorLemoine, NR
dc.contributor.authorChelala, C
dc.date.accessioned2015-02-23T08:53:17Z
dc.date.accessioned2015-03-06T10:40:26Z
dc.date.accessioned2015-03-06T10:40:34Z
dc.date.issued2014
dc.date.issued2014
dc.date.issued2014
dc.date.issued2014
dc.date.issued2014
dc.date.issued2014
dc.date.issued2014
dc.date.issued2014
dc.identifier.urihttp://qmro.qmul.ac.uk/jspui/handle/123456789/6841
dc.description© 2014 Haider et al.; licensee BioMed Central. 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.
dc.description.abstractBACKGROUND: Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options. METHODS: Using publicly available mRNA abundance datasets, we performed a large retrospective meta-analysis on 466 PDAC patients to discover prognostic gene signatures. These signatures were trained on two clinical cohorts (n = 70), and validated on four independent clinical cohorts (n = 246). Further validation of the identified gene signature was performed using quantitative real-time RT-PCR. RESULTS: We identified 225 candidate prognostic genes. Using these, a 36-gene signature was discovered and validated on fully independent clinical cohorts (hazard ratio (HR) = 2.06, 95% confidence interval (CI) = 1.51 to 2.81, P = 3.62 × 10(-6), n = 246). This signature serves as a good alternative prognostic stratification marker compared to tumour grade (HR = 2.05, 95% CI = 1.45 to 2.88, P = 3.18 × 10(-5)) and tumour node metastasis (TNM) stage (HR = 1.13, 95% CI = 0.66 to 1.94, P = 0.67). Upon multivariate analysis with adjustment for TNM stage and tumour grade, the 36-gene signature remained an independent prognostic predictor of clinical outcome (HR = 2.21, 95% CI = 1.17 to 4.16, P = 0.01). Univariate assessment revealed higher expression of ITGA5, SEMA3A, KIF4A, IL20RB, SLC20A1, CDC45, PXN, SSX3 and TMEM26 was correlated with shorter survival while B3GNT1, NOSTRIN and CADPS down-regulation was associated with poor outcome. CONCLUSIONS: Our 36-gene classifier is able to prognosticate PDAC independent of patient cohort and microarray platforms. Further work on the functional roles, downstream events and interactions of the signature genes is likely to reveal true molecular candidates for PDAC therapeutics.
dc.format.extent105 - ?
dc.languageeng
dc.relation.ispartofGenome Med
dc.relation.replaceshttp://qmro.qmul.ac.uk/jspui/handle/123456789/6601
dc.relation.replaces123456789/6601
dc.relation.replaceshttp://qmro.qmul.ac.uk/jspui/handle/123456789/6840
dc.relation.replaces123456789/6840
dc.titleA multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.
dc.typeJournal Article
dc.identifier.doi10.1186/s13073-014-0105-3
dc.relation.isPartOfGenome Med
dc.relation.isPartOfGenome Med
dc.relation.isPartOfGenome Med
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/25587357
pubs.issue12
pubs.organisational-group/Queen Mary University of London
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Barts Cancer Institute
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Barts Cancer Institute/Barts Cancer Institute - Research Students
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Barts Cancer Institute/Haemato-Oncology
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Barts Cancer Institute/Medical Oncology
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Barts Cancer Institute/Molecular Oncology
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Barts Cancer Institute/Tumour Biology
pubs.organisational-group/Queen Mary University of London/Faculty Reporting - Research Students
pubs.organisational-group/Queen Mary University of London/Faculty Reporting - Research Students/Faculty of Medicine & Dentistry PGRs
pubs.publication-statusPublished online
pubs.volume6


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