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

Abstract 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Stefan Porubsky, Malin Nientiedt, Maximilian C. Kriegmair, Jörn-Helge Heinrich Siemoneit, Roger Sandhoff, Richard Jennemann, Hendrik Borgmann, Timo Gaiser, Cleo-Aron Weis, Philipp Erben, Thomas Hielscher, Zoran V. Popovic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/08f451bc6274482e842f3d75e75a5ff8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:08f451bc6274482e842f3d75e75a5ff8
record_format	dspace
spelling	oai:doaj.org-article:08f451bc6274482e842f3d75e75a5ff82021-12-02T15:49:31ZThe prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma10.1038/s41598-021-90381-62045-2322https://doaj.org/article/08f451bc6274482e842f3d75e75a5ff82021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90381-6https://doaj.org/toc/2045-2322Abstract 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.Stefan PorubskyMalin NientiedtMaximilian C. KriegmairJörn-Helge Heinrich SiemoneitRoger SandhoffRichard JennemannHendrik BorgmannTimo GaiserCleo-Aron WeisPhilipp ErbenThomas HielscherZoran V. PopovicNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stefan Porubsky Malin Nientiedt Maximilian C. Kriegmair Jörn-Helge Heinrich Siemoneit Roger Sandhoff Richard Jennemann Hendrik Borgmann Timo Gaiser Cleo-Aron Weis Philipp Erben Thomas Hielscher Zoran V. Popovic The prognostic value of galactosylceramide-sulfotransferase (Gal3ST1) in human renal cell carcinoma
description	Abstract 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.
format	article
author	Stefan Porubsky Malin Nientiedt Maximilian C. Kriegmair Jörn-Helge Heinrich Siemoneit Roger Sandhoff Richard Jennemann Hendrik Borgmann Timo Gaiser Cleo-Aron Weis Philipp Erben Thomas Hielscher Zoran V. Popovic
author_facet	Stefan Porubsky Malin Nientiedt Maximilian C. Kriegmair Jörn-Helge Heinrich Siemoneit Roger Sandhoff Richard Jennemann Hendrik Borgmann Timo Gaiser Cleo-Aron Weis Philipp Erben Thomas Hielscher Zoran V. Popovic
author_sort	Stefan Porubsky
title	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_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_sort	prognostic value of galactosylceramide-sulfotransferase (gal3st1) in human renal cell carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/08f451bc6274482e842f3d75e75a5ff8
work_keys_str_mv	AT stefanporubsky theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT malinnientiedt theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT maximilianckriegmair theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT jornhelgeheinrichsiemoneit theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT rogersandhoff theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT richardjennemann theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT hendrikborgmann theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT timogaiser theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT cleoaronweis theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT philipperben theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT thomashielscher theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT zoranvpopovic theprognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT stefanporubsky prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT malinnientiedt prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT maximilianckriegmair prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT jornhelgeheinrichsiemoneit prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT rogersandhoff prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT richardjennemann prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT hendrikborgmann prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT timogaiser prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT cleoaronweis prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT philipperben prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT thomashielscher prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma AT zoranvpopovic prognosticvalueofgalactosylceramidesulfotransferasegal3st1inhumanrenalcellcarcinoma
_version_	1718385671490502656

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

Ejemplares similares