Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma

Abstract Metabolic reprogramming of tumor cells and the increase of glucose uptake is one of the hallmarks of cancer. In order to identify metabolic pathways activated in leiomyosarcoma (LMS), we analyzed transcriptomic profiles of distinct subtypes of LMS in several datasets. Primary, recurrent and...

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Autores principales:	Angela Tolwani, Magdalena Matusiak, Nam Bui, Erna Forgó, Sushama Varma, Lucia Baratto, Andrei Iagaru, Alexander J. Lazar, Matt van de Rijn, Joanna Przybyl
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/fc3aae85255741adb708ed42e7403540
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spelling	oai:doaj.org-article:fc3aae85255741adb708ed42e74035402021-12-02T14:29:05ZPrognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma10.1038/s41525-021-00193-w2056-7944https://doaj.org/article/fc3aae85255741adb708ed42e74035402021-05-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00193-whttps://doaj.org/toc/2056-7944Abstract Metabolic reprogramming of tumor cells and the increase of glucose uptake is one of the hallmarks of cancer. In order to identify metabolic pathways activated in leiomyosarcoma (LMS), we analyzed transcriptomic profiles of distinct subtypes of LMS in several datasets. Primary, recurrent and metastatic tumors in the subtype 2 of LMS showed consistent enrichment of genes involved in hexosamine biosynthesis pathway (HBP). We demonstrated that glutamine-fructose-6-phosphate transaminase 2 (GFPT2), the rate-limiting enzyme in HBP, is expressed on protein level in a subset of LMS and the expression of this enzyme is frequently retained in patient-matched primary and metastatic tumors. In a new independent cohort of 327 patients, we showed that GFPT2 is associated with poor outcome of uterine LMS but not extra-uterine LMS. Based on the analysis of a small group of patients studied by 18F-FDG-PET imaging, we propose that strong expression of GFPT2 in primary LMS may be associated with high metabolic activity. Our data suggest that HBP is a potential new therapeutic target in one of the subtypes of LMS.Angela TolwaniMagdalena MatusiakNam BuiErna ForgóSushama VarmaLucia BarattoAndrei IagaruAlexander J. LazarMatt van de RijnJoanna PrzybylNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Angela Tolwani Magdalena Matusiak Nam Bui Erna Forgó Sushama Varma Lucia Baratto Andrei Iagaru Alexander J. Lazar Matt van de Rijn Joanna Przybyl Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma
description	Abstract Metabolic reprogramming of tumor cells and the increase of glucose uptake is one of the hallmarks of cancer. In order to identify metabolic pathways activated in leiomyosarcoma (LMS), we analyzed transcriptomic profiles of distinct subtypes of LMS in several datasets. Primary, recurrent and metastatic tumors in the subtype 2 of LMS showed consistent enrichment of genes involved in hexosamine biosynthesis pathway (HBP). We demonstrated that glutamine-fructose-6-phosphate transaminase 2 (GFPT2), the rate-limiting enzyme in HBP, is expressed on protein level in a subset of LMS and the expression of this enzyme is frequently retained in patient-matched primary and metastatic tumors. In a new independent cohort of 327 patients, we showed that GFPT2 is associated with poor outcome of uterine LMS but not extra-uterine LMS. Based on the analysis of a small group of patients studied by 18F-FDG-PET imaging, we propose that strong expression of GFPT2 in primary LMS may be associated with high metabolic activity. Our data suggest that HBP is a potential new therapeutic target in one of the subtypes of LMS.
format	article
author	Angela Tolwani Magdalena Matusiak Nam Bui Erna Forgó Sushama Varma Lucia Baratto Andrei Iagaru Alexander J. Lazar Matt van de Rijn Joanna Przybyl
author_facet	Angela Tolwani Magdalena Matusiak Nam Bui Erna Forgó Sushama Varma Lucia Baratto Andrei Iagaru Alexander J. Lazar Matt van de Rijn Joanna Przybyl
author_sort	Angela Tolwani
title	Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma
title_short	Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma
title_full	Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma
title_fullStr	Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma
title_full_unstemmed	Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma
title_sort	prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fc3aae85255741adb708ed42e7403540
work_keys_str_mv	AT angelatolwani prognosticrelevanceofthehexosaminebiosynthesispathwayactivationinleiomyosarcoma AT magdalenamatusiak prognosticrelevanceofthehexosaminebiosynthesispathwayactivationinleiomyosarcoma AT nambui prognosticrelevanceofthehexosaminebiosynthesispathwayactivationinleiomyosarcoma AT ernaforgo prognosticrelevanceofthehexosaminebiosynthesispathwayactivationinleiomyosarcoma AT sushamavarma prognosticrelevanceofthehexosaminebiosynthesispathwayactivationinleiomyosarcoma AT luciabaratto prognosticrelevanceofthehexosaminebiosynthesispathwayactivationinleiomyosarcoma AT andreiiagaru prognosticrelevanceofthehexosaminebiosynthesispathwayactivationinleiomyosarcoma AT alexanderjlazar prognosticrelevanceofthehexosaminebiosynthesispathwayactivationinleiomyosarcoma AT mattvanderijn prognosticrelevanceofthehexosaminebiosynthesispathwayactivationinleiomyosarcoma AT joannaprzybyl prognosticrelevanceofthehexosaminebiosynthesispathwayactivationinleiomyosarcoma
_version_	1718391288866275328

Prognostic relevance of the hexosamine biosynthesis pathway activation in leiomyosarcoma

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