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dc.contributor.authorLaird, Alexander
dc.contributor.authorO'Mahony, Fiach C.
dc.contributor.authorNanda, Jyoti
dc.contributor.authorRiddick, Antony C. P.
dc.contributor.authorO'Donnell, Marie
dc.contributor.authorHarrison, David J.
dc.contributor.authorStewart, Grant D.
dc.date.accessioned2014-07-22T11:01:06Z
dc.date.available2014-07-22T11:01:06Z
dc.date.issued2013-04-05
dc.identifier.citationLaird , A , O'Mahony , F C , Nanda , J , Riddick , A C P , O'Donnell , M , Harrison , D J & Stewart , G D 2013 , ' Differential expression of prognostic proteomic markers in primary tumour, venous tumour thrombus and metastatic renal cell cancer tissue and correlation with patient outcome ' , PLoS ONE , vol. 8 , no. 4 , e60483 . https://doi.org/10.1371/journal.pone.0060483en
dc.identifier.issn1932-6203
dc.identifier.otherPURE: 134422946
dc.identifier.otherPURE UUID: 444c85ba-c7e5-4dd4-b0ee-2b4ec96ba011
dc.identifier.otherWOS: 000319109800056
dc.identifier.otherScopus: 84875917518
dc.identifier.otherORCID: /0000-0001-9041-9988/work/64034207
dc.identifier.urihttp://hdl.handle.net/10023/5062
dc.descriptionThe work of the author AL is funded by The Royal College of Surgeons of Edinburgh Robertson’s Trust, The Melville Trust for the care and cure of cancer and The Medical Research Council Scottish Clinical Pharmacology and Pathology Programme. The work of authors FCO, JN, ACPR, DJH and GDS mentioned above is funded by the Chief Scientist Office, grant number ETM37, and supported by Chief Scientist Funded Health Sciences Scotland and the Cancer Research UK Experimental Cancer Medicine Centre.en
dc.description.abstractRenal cell carcinoma (RCC) is the most deadly of urological malignancies. Metastatic disease affects one third of patients at diagnosis with a further third developing metastatic disease after extirpative surgery. Heterogeneity in the clinical course ensures predicting metastasis is notoriously difficult, despite the routine use of prognostic clinico-pathological parameters in risk stratification. With greater understanding of pathways involved in disease pathogenesis, a number of biomarkers have been shown to have prognostic significance, including Ki67, p53, vascular endothelial growth factor receptor 1 (VEGFR1) and ligand D (VEGFD), SNAIL and SLUG. Previous pathway analysis has been from study of the primary tumour, with little attention to the metastatic tumours which are the focus of targeted molecular therapies. As such, in this study a tissue microarray from 177 patients with primary renal tumour, renal vein tumour thrombus and/or RCC metastasis has been created and used with Automated Quantitative Analysis (AQUA) of immunofluorescence to study the prognostic significance of these markers in locally advanced and metastatic disease. Furthermore, this has allowed assessment of differential protein expression between the primary tumours, renal vein tumour thrombi and metastases. The results demonstrate that clinico-pathological parameters remain the most significant predictors of cancer specific survival; however, high VEGFR1 or VEGFD can predict poor cancer specific survival on univariate analysis for locally advanced and metastatic disease. There was significantly greater expression of Ki67, p53, VEGFR1, SLUG and SNAIL in the metastases compared with the primary tumours and renal vein tumour thrombi. With the exception of p53, these differences in protein expression have not been shown previously in RCC. This confirms the importance of proliferation, angiogenesis and epithelial to mesenchymal transition in the pathogenesis and metastasis of RCC. Importantly, this work highlights the need for further pathway analysis of metastatic tumours for overcoming drug resistance and developing new therapies.
dc.format.extent14
dc.language.isoeng
dc.relation.ispartofPLoS ONEen
dc.rightsCopyright: © 2013 Laird et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectEndothelial growth-factoren
dc.subjectP53 protein expressionen
dc.subjectMessenger-RNA expressionen
dc.subjectClear-cellen
dc.subjectLymph-nodeen
dc.subjectClinicopathological parametersen
dc.subjectPathological featuresen
dc.subjectRadical nephrectomyen
dc.subjectColorectal-canceren
dc.subjectInterferon-alphaen
dc.subjectR Medicine (General)en
dc.subject.lccR1en
dc.titleDifferential expression of prognostic proteomic markers in primary tumour, venous tumour thrombus and metastatic renal cell cancer tissue and correlation with patient outcomeen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0060483
dc.description.statusPeer revieweden


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