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Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma

BACKGROUND: Plasma glycosaminoglycan (GAG) measurements, when aggregated into diagnostic scores, accurately distinguish metastatic clear-cell renal cell carcinoma (RCC) from healthy samples and correlate with prognosis. However, it is unknown if GAG scores can detect RCC in earlier stages or if they...

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Autores principales: Gatto, Francesco, Blum, Kyle A., Hosseini, Seyedeh Shaghayegh, Ghanaat, Mazyar, Kashan, Mahyar, Maccari, Francesca, Galeotti, Fabio, Hsieh, James J., Volpi, Nicola, Hakimi, A. Ari, Nielsen, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253162/
https://www.ncbi.nlm.nih.gov/pubmed/31158075
http://dx.doi.org/10.1016/j.euo.2018.04.015
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author Gatto, Francesco
Blum, Kyle A.
Hosseini, Seyedeh Shaghayegh
Ghanaat, Mazyar
Kashan, Mahyar
Maccari, Francesca
Galeotti, Fabio
Hsieh, James J.
Volpi, Nicola
Hakimi, A. Ari
Nielsen, Jens
author_facet Gatto, Francesco
Blum, Kyle A.
Hosseini, Seyedeh Shaghayegh
Ghanaat, Mazyar
Kashan, Mahyar
Maccari, Francesca
Galeotti, Fabio
Hsieh, James J.
Volpi, Nicola
Hakimi, A. Ari
Nielsen, Jens
author_sort Gatto, Francesco
collection PubMed
description BACKGROUND: Plasma glycosaminoglycan (GAG) measurements, when aggregated into diagnostic scores, accurately distinguish metastatic clear-cell renal cell carcinoma (RCC) from healthy samples and correlate with prognosis. However, it is unknown if GAG scores can detect RCC in earlier stages or if they correlate with prognosis after surgery. OBJECTIVE: To explore the sensitivity and specificity of plasma GAGs for detection of early-stage RCC and prediction of recurrence and death after RCC surgery. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective case-control study consisting of a consecutive series of 175 RCC patients surgically treated between May 2011 and February 2014 and 19 healthy controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Plasma GAGs in preoperative and postoperative RCC and healthy samples were measured using capillary electrophoresis with laser-induced fluorescence in a single blinded laboratory. A discovery set was first analyzed to update the historical GAG score. The sensitivity of the new GAG score for RCC detection versus healthy subjects was validated using the remaining samples. The correlation of the new GAG score to histopathologic variables, overall survival, and recurrence-free survival was evaluated using nonparametric and log-rank tests and multivariable Cox regression analyses. RESULTS AND LIMITATIONS: The RCC cohort included 94 stage I, 58 stage II–III, and 22 stage IV cases. In the first discovery set (n = 67), the new GAG score distinguished RCC from healthy samples with an area under the receiver operating characteristic curve (AUC) of 0.999. In the validation set (n = 108), the GAG score achieved an AUC of 0.991, with 93.5% sensitivity. GAG scores were elevated in RCC compared to healthy samples, irrespective of and uncorrelated to stage, grade, histology, age, or gender. The total chondroitin sulfate concentration was an independent prognostic factor for both overall and recurrence-free survival (hazard ratios 1.51 and 1.25) with high concordance when combined with variables available at pathologic diagnosis (C-index 0.926 and 0.849) or preoperatively (C-index 0.846 and 0.736). Limitations of the study include its retrospective nature and moderate variability in GAG laboratory measurements. CONCLUSIONS: Plasma GAGs are highly sensitive diagnostic and prognostic biomarkers in surgically treated RCC independent of stage, grade, or histology. Prospective validation studies on GAG scores for early detection, prediction, and surveillance for RCC recurrence are thus warranted. PATIENT SUMMARY: In this study, we examined if a new molecular blood test can detect renal cell carcinoma in the early stages and predict if the cancer might relapse after surgery.
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spelling pubmed-82531622021-07-02 Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma Gatto, Francesco Blum, Kyle A. Hosseini, Seyedeh Shaghayegh Ghanaat, Mazyar Kashan, Mahyar Maccari, Francesca Galeotti, Fabio Hsieh, James J. Volpi, Nicola Hakimi, A. Ari Nielsen, Jens Eur Urol Oncol Article BACKGROUND: Plasma glycosaminoglycan (GAG) measurements, when aggregated into diagnostic scores, accurately distinguish metastatic clear-cell renal cell carcinoma (RCC) from healthy samples and correlate with prognosis. However, it is unknown if GAG scores can detect RCC in earlier stages or if they correlate with prognosis after surgery. OBJECTIVE: To explore the sensitivity and specificity of plasma GAGs for detection of early-stage RCC and prediction of recurrence and death after RCC surgery. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective case-control study consisting of a consecutive series of 175 RCC patients surgically treated between May 2011 and February 2014 and 19 healthy controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Plasma GAGs in preoperative and postoperative RCC and healthy samples were measured using capillary electrophoresis with laser-induced fluorescence in a single blinded laboratory. A discovery set was first analyzed to update the historical GAG score. The sensitivity of the new GAG score for RCC detection versus healthy subjects was validated using the remaining samples. The correlation of the new GAG score to histopathologic variables, overall survival, and recurrence-free survival was evaluated using nonparametric and log-rank tests and multivariable Cox regression analyses. RESULTS AND LIMITATIONS: The RCC cohort included 94 stage I, 58 stage II–III, and 22 stage IV cases. In the first discovery set (n = 67), the new GAG score distinguished RCC from healthy samples with an area under the receiver operating characteristic curve (AUC) of 0.999. In the validation set (n = 108), the GAG score achieved an AUC of 0.991, with 93.5% sensitivity. GAG scores were elevated in RCC compared to healthy samples, irrespective of and uncorrelated to stage, grade, histology, age, or gender. The total chondroitin sulfate concentration was an independent prognostic factor for both overall and recurrence-free survival (hazard ratios 1.51 and 1.25) with high concordance when combined with variables available at pathologic diagnosis (C-index 0.926 and 0.849) or preoperatively (C-index 0.846 and 0.736). Limitations of the study include its retrospective nature and moderate variability in GAG laboratory measurements. CONCLUSIONS: Plasma GAGs are highly sensitive diagnostic and prognostic biomarkers in surgically treated RCC independent of stage, grade, or histology. Prospective validation studies on GAG scores for early detection, prediction, and surveillance for RCC recurrence are thus warranted. PATIENT SUMMARY: In this study, we examined if a new molecular blood test can detect renal cell carcinoma in the early stages and predict if the cancer might relapse after surgery. 2018-06-13 2018-10 /pmc/articles/PMC8253162/ /pubmed/31158075 http://dx.doi.org/10.1016/j.euo.2018.04.015 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Gatto, Francesco
Blum, Kyle A.
Hosseini, Seyedeh Shaghayegh
Ghanaat, Mazyar
Kashan, Mahyar
Maccari, Francesca
Galeotti, Fabio
Hsieh, James J.
Volpi, Nicola
Hakimi, A. Ari
Nielsen, Jens
Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma
title Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma
title_full Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma
title_fullStr Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma
title_full_unstemmed Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma
title_short Plasma Glycosaminoglycans as Diagnostic and Prognostic Biomarkers in Surgically Treated Renal Cell Carcinoma
title_sort plasma glycosaminoglycans as diagnostic and prognostic biomarkers in surgically treated renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253162/
https://www.ncbi.nlm.nih.gov/pubmed/31158075
http://dx.doi.org/10.1016/j.euo.2018.04.015
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