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Differential Expression of Prognostic Proteomic Markers in Primary Tumour, Venous Tumour Thrombus and Metastatic Renal Cell Cancer Tissue and Correlation with Patient Outcome

Renal 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 diff...

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Autores principales: Laird, Alexander, O’Mahony, Fiach C., Nanda, Jyoti, Riddick, Antony C. P., O’Donnell, Marie, Harrison, David J., Stewart, Grant D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618228/
https://www.ncbi.nlm.nih.gov/pubmed/23577117
http://dx.doi.org/10.1371/journal.pone.0060483
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author Laird, Alexander
O’Mahony, Fiach C.
Nanda, Jyoti
Riddick, Antony C. P.
O’Donnell, Marie
Harrison, David J.
Stewart, Grant D.
author_facet Laird, Alexander
O’Mahony, Fiach C.
Nanda, Jyoti
Riddick, Antony C. P.
O’Donnell, Marie
Harrison, David J.
Stewart, Grant D.
author_sort Laird, Alexander
collection PubMed
description Renal 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.
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spelling pubmed-36182282013-04-10 Differential Expression of Prognostic Proteomic Markers in Primary Tumour, Venous Tumour Thrombus and Metastatic Renal Cell Cancer Tissue and Correlation with Patient Outcome Laird, Alexander O’Mahony, Fiach C. Nanda, Jyoti Riddick, Antony C. P. O’Donnell, Marie Harrison, David J. Stewart, Grant D. PLoS One Research Article Renal 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. Public Library of Science 2013-04-05 /pmc/articles/PMC3618228/ /pubmed/23577117 http://dx.doi.org/10.1371/journal.pone.0060483 Text en © 2013 Laird et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Laird, Alexander
O’Mahony, Fiach C.
Nanda, Jyoti
Riddick, Antony C. P.
O’Donnell, Marie
Harrison, David J.
Stewart, Grant D.
Differential Expression of Prognostic Proteomic Markers in Primary Tumour, Venous Tumour Thrombus and Metastatic Renal Cell Cancer Tissue and Correlation with Patient Outcome
title Differential Expression of Prognostic Proteomic Markers in Primary Tumour, Venous Tumour Thrombus and Metastatic Renal Cell Cancer Tissue and Correlation with Patient Outcome
title_full Differential Expression of Prognostic Proteomic Markers in Primary Tumour, Venous Tumour Thrombus and Metastatic Renal Cell Cancer Tissue and Correlation with Patient Outcome
title_fullStr Differential Expression of Prognostic Proteomic Markers in Primary Tumour, Venous Tumour Thrombus and Metastatic Renal Cell Cancer Tissue and Correlation with Patient Outcome
title_full_unstemmed Differential Expression of Prognostic Proteomic Markers in Primary Tumour, Venous Tumour Thrombus and Metastatic Renal Cell Cancer Tissue and Correlation with Patient Outcome
title_short Differential Expression of Prognostic Proteomic Markers in Primary Tumour, Venous Tumour Thrombus and Metastatic Renal Cell Cancer Tissue and Correlation with Patient Outcome
title_sort differential expression of prognostic proteomic markers in primary tumour, venous tumour thrombus and metastatic renal cell cancer tissue and correlation with patient outcome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618228/
https://www.ncbi.nlm.nih.gov/pubmed/23577117
http://dx.doi.org/10.1371/journal.pone.0060483
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