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Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma

BACKGROUND: No circulating markers are routinely used for renal cancer. The objective of this pilot study was to investigate whether conditioned media (CM) from renal cancer cell lines contains potential biomarkers that, when measured in clinical fluids, have diagnostic or prognostic utility. METHOD...

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Autores principales: Vasudev, N S, Sim, S, Cairns, D A, Ferguson, R E, Craven, R A, Stanley, A, Cartledge, J, Thompson, D, Selby, P J, Banks, R E
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768081/
https://www.ncbi.nlm.nih.gov/pubmed/19789534
http://dx.doi.org/10.1038/sj.bjc.6605250
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author Vasudev, N S
Sim, S
Cairns, D A
Ferguson, R E
Craven, R A
Stanley, A
Cartledge, J
Thompson, D
Selby, P J
Banks, R E
author_facet Vasudev, N S
Sim, S
Cairns, D A
Ferguson, R E
Craven, R A
Stanley, A
Cartledge, J
Thompson, D
Selby, P J
Banks, R E
author_sort Vasudev, N S
collection PubMed
description BACKGROUND: No circulating markers are routinely used for renal cancer. The objective of this pilot study was to investigate whether conditioned media (CM) from renal cancer cell lines contains potential biomarkers that, when measured in clinical fluids, have diagnostic or prognostic utility. METHODS: Comparative 2D PAGE profiling of CM from renal cell carcinoma (RCC) and normal renal cultures identified cathepsin D that was subsequently validated in urine samples from 239 patients and healthy and benign disease subjects. RESULTS: Urinary cathepsin D was found to be significantly associated with overall (OS) (hazard ratio, HR, 1.33, 95%CI [1.09–1.63], P=0.005) and cancer-specific survival (HR 1.36, 95%CI [1.07–1.74], P=0.013) in RCC patients on univariate analysis. An optimal cut point (211 ng ml(−1) μmolCr(−1)) around which to stratify patients by OS was determined. Five-year OS equal to/above and below this value was 47.0% (95%CI 35.4%, 62.4%) and 60.9% (48.8%, 76.0%), respectively. On multivariable analysis using pre-operative variables, cathepsin D showed some evidence of independent prognostic value for OS (likelihood ratio test P-value=0.056) although requiring further validation in larger patient numbers with sufficient statistical power to determine independent significance. CONCLUSION: These data establish an important proof of principle and show the potential of proteomics-based studies. Cathepsin D may be of value as a pre-operative urinary biomarker for RCC, alone or in combination.
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spelling pubmed-27680812010-10-06 Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma Vasudev, N S Sim, S Cairns, D A Ferguson, R E Craven, R A Stanley, A Cartledge, J Thompson, D Selby, P J Banks, R E Br J Cancer Molecular Diagnostics BACKGROUND: No circulating markers are routinely used for renal cancer. The objective of this pilot study was to investigate whether conditioned media (CM) from renal cancer cell lines contains potential biomarkers that, when measured in clinical fluids, have diagnostic or prognostic utility. METHODS: Comparative 2D PAGE profiling of CM from renal cell carcinoma (RCC) and normal renal cultures identified cathepsin D that was subsequently validated in urine samples from 239 patients and healthy and benign disease subjects. RESULTS: Urinary cathepsin D was found to be significantly associated with overall (OS) (hazard ratio, HR, 1.33, 95%CI [1.09–1.63], P=0.005) and cancer-specific survival (HR 1.36, 95%CI [1.07–1.74], P=0.013) in RCC patients on univariate analysis. An optimal cut point (211 ng ml(−1) μmolCr(−1)) around which to stratify patients by OS was determined. Five-year OS equal to/above and below this value was 47.0% (95%CI 35.4%, 62.4%) and 60.9% (48.8%, 76.0%), respectively. On multivariable analysis using pre-operative variables, cathepsin D showed some evidence of independent prognostic value for OS (likelihood ratio test P-value=0.056) although requiring further validation in larger patient numbers with sufficient statistical power to determine independent significance. CONCLUSION: These data establish an important proof of principle and show the potential of proteomics-based studies. Cathepsin D may be of value as a pre-operative urinary biomarker for RCC, alone or in combination. Nature Publishing Group 2009-10-06 2009-09-29 /pmc/articles/PMC2768081/ /pubmed/19789534 http://dx.doi.org/10.1038/sj.bjc.6605250 Text en Copyright © 2009 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular Diagnostics
Vasudev, N S
Sim, S
Cairns, D A
Ferguson, R E
Craven, R A
Stanley, A
Cartledge, J
Thompson, D
Selby, P J
Banks, R E
Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma
title Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma
title_full Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma
title_fullStr Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma
title_full_unstemmed Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma
title_short Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma
title_sort pre-operative urinary cathepsin d is associated with survival in patients with renal cell carcinoma
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768081/
https://www.ncbi.nlm.nih.gov/pubmed/19789534
http://dx.doi.org/10.1038/sj.bjc.6605250
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