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The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma

Renal cell carcinoma (RCC) is the deadliest primary genitourinary malignancy typically associated with asymptomatic initial presentation and poorly predictable survival. Next to established risk factors, tumor microenvironment may alter metastatic capacity and immune landscape. Due to their high con...

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Autores principales: Porubsky, Stefan, Nientiedt, Malin, Kriegmair, Maximilian C., Siemoneit, Jörn-Helge Heinrich, Sandhoff, Roger, Jennemann, Richard, Borgmann, Hendrik, Gaiser, Timo, Weis, Cleo-Aron, Erben, Philipp, Hielscher, Thomas, Popovic, Zoran V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149814/
https://www.ncbi.nlm.nih.gov/pubmed/34035403
http://dx.doi.org/10.1038/s41598-021-90381-6
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author Porubsky, Stefan
Nientiedt, Malin
Kriegmair, Maximilian C.
Siemoneit, Jörn-Helge Heinrich
Sandhoff, Roger
Jennemann, Richard
Borgmann, Hendrik
Gaiser, Timo
Weis, Cleo-Aron
Erben, Philipp
Hielscher, Thomas
Popovic, Zoran V.
author_facet Porubsky, Stefan
Nientiedt, Malin
Kriegmair, Maximilian C.
Siemoneit, Jörn-Helge Heinrich
Sandhoff, Roger
Jennemann, Richard
Borgmann, Hendrik
Gaiser, Timo
Weis, Cleo-Aron
Erben, Philipp
Hielscher, Thomas
Popovic, Zoran V.
author_sort Porubsky, Stefan
collection PubMed
description Renal cell carcinoma (RCC) is the deadliest primary genitourinary malignancy typically associated with asymptomatic initial presentation and poorly predictable survival. Next to established risk factors, tumor microenvironment may alter metastatic capacity and immune landscape. Due to their high concentrations, sulfoglycolipids (sulfatides) were among the first well-described antigens in RCC that are associated with worse prognosis. As sulfatide detection in routine diagnostics is not possible, we aimed to test the prognostic value of its protein counterpart, sulfatide-producing enzyme Gal3ST1. We performed retrospective long-term follow up analysis of Gal3ST1 expression as prognostic risk factor in a representative RCC patient cohort. We observed differentially regulated Gal3ST1 expression in all RCC types, being significantly more associated with clear cell RCC than to chromophobe RCC (p = 0.001). Surprisingly, in contrast to published observations from in vitro models, we could not confirm an association between Gal3ST1 expression and a malignant clinical behaviour of the RCC. In our cohort, Gal3ST1 did not significantly influence progression-free survival (Hazard Ratio (HR): 1.7 95% CI (0.6–4.9), p = 0.327). Particularly after adjusting for histology, T-stage, N-status and M-status at baseline, we observed no independent prognostic effect (HR = 1.0 95% CI (0.3–3.3), p = 0.96). The analysis of Gal3ST1 mRNA expression in a TCGA dataset supported the results of our cohort. Thus, Gal3ST1 might help to differentiate between chromophobe RCC and other frequent RCC entities but—despite previously published data from cell culture models—does not qualify as a prognostic marker for RCC. Further investigation of regulatory mechanisms of sulfatide metabolism in human RCC microenvironment is necessary to understand the role of this quantitatively prominent glycosphingolipid in RCC progression.
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spelling pubmed-81498142021-05-26 The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma Porubsky, Stefan Nientiedt, Malin Kriegmair, Maximilian C. Siemoneit, Jörn-Helge Heinrich Sandhoff, Roger Jennemann, Richard Borgmann, Hendrik Gaiser, Timo Weis, Cleo-Aron Erben, Philipp Hielscher, Thomas Popovic, Zoran V. Sci Rep Article Renal cell carcinoma (RCC) is the deadliest primary genitourinary malignancy typically associated with asymptomatic initial presentation and poorly predictable survival. Next to established risk factors, tumor microenvironment may alter metastatic capacity and immune landscape. Due to their high concentrations, sulfoglycolipids (sulfatides) were among the first well-described antigens in RCC that are associated with worse prognosis. As sulfatide detection in routine diagnostics is not possible, we aimed to test the prognostic value of its protein counterpart, sulfatide-producing enzyme Gal3ST1. We performed retrospective long-term follow up analysis of Gal3ST1 expression as prognostic risk factor in a representative RCC patient cohort. We observed differentially regulated Gal3ST1 expression in all RCC types, being significantly more associated with clear cell RCC than to chromophobe RCC (p = 0.001). Surprisingly, in contrast to published observations from in vitro models, we could not confirm an association between Gal3ST1 expression and a malignant clinical behaviour of the RCC. In our cohort, Gal3ST1 did not significantly influence progression-free survival (Hazard Ratio (HR): 1.7 95% CI (0.6–4.9), p = 0.327). Particularly after adjusting for histology, T-stage, N-status and M-status at baseline, we observed no independent prognostic effect (HR = 1.0 95% CI (0.3–3.3), p = 0.96). The analysis of Gal3ST1 mRNA expression in a TCGA dataset supported the results of our cohort. Thus, Gal3ST1 might help to differentiate between chromophobe RCC and other frequent RCC entities but—despite previously published data from cell culture models—does not qualify as a prognostic marker for RCC. Further investigation of regulatory mechanisms of sulfatide metabolism in human RCC microenvironment is necessary to understand the role of this quantitatively prominent glycosphingolipid in RCC progression. Nature Publishing Group UK 2021-05-25 /pmc/articles/PMC8149814/ /pubmed/34035403 http://dx.doi.org/10.1038/s41598-021-90381-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Porubsky, Stefan
Nientiedt, Malin
Kriegmair, Maximilian C.
Siemoneit, Jörn-Helge Heinrich
Sandhoff, Roger
Jennemann, Richard
Borgmann, Hendrik
Gaiser, Timo
Weis, Cleo-Aron
Erben, Philipp
Hielscher, Thomas
Popovic, Zoran V.
The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma
title The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma
title_full The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma
title_fullStr The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma
title_full_unstemmed The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma
title_short The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma
title_sort prognostic value of galactosylceramide-sulfotransferase (gal3st1) in human renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149814/
https://www.ncbi.nlm.nih.gov/pubmed/34035403
http://dx.doi.org/10.1038/s41598-021-90381-6
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