Molecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome

Abstract Deregulated cellular energetics is formally incorporated as an emerging hallmark of cancer, however little is known about its processes in myelodysplastic syndromes (MDS). Using transcriptomic data of CD34+ cells from 159 MDS patients and 17 healthy donors, we selected 37 genes involved in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Juan L. Coelho-Silva, Douglas R. A. Silveira, Diego A. Pereira-Martins, Cesar A. O. Rojas, Antonio R. Lucena-Araujo, Eduardo M. Rego, João A. Machado-Neto, Israel Bendit, Vanderson Rocha, Fabiola Traina
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ba9e4b1885747c1968531cbed9acd10
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8ba9e4b1885747c1968531cbed9acd10
record_format	dspace
spelling	oai:doaj.org-article:8ba9e4b1885747c1968531cbed9acd102021-12-02T15:23:39ZMolecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome10.1038/s41598-020-80918-62045-2322https://doaj.org/article/8ba9e4b1885747c1968531cbed9acd102021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80918-6https://doaj.org/toc/2045-2322Abstract Deregulated cellular energetics is formally incorporated as an emerging hallmark of cancer, however little is known about its processes in myelodysplastic syndromes (MDS). Using transcriptomic data of CD34+ cells from 159 MDS patients and 17 healthy donors, we selected 37 genes involved in cellular energetics and interrogated about its clinical and prognostic functions. Based on the low expression of ACLY, ANPEP, and PANK1, as well as high expression of PKM and SLC25A5, we constructed our Molecular-Based Score (MBS), that efficiently discriminated patients at three risks groups: favourable risk (n = 28; 3-year overall survival (OS): 100%); intermediate (n = 60; 76% [62–93%]) and adverse (n = 71; 35% [17–61%]). Adverse MBS risk was independently associated with inferior OS (HR = 10.1 [95% CI 1.26–81]; P = 0.029) in multivariable analysis using age, gender and the revised international prognostic score system as confounders. Transcriptional signature revealed that Favourable- and intermediate-risk patients presented enriched molecular programs related to mature myeloid progenitors, cell cycle progression, and oxidative phosphorylation, indicating that this cells differs in their origin, metabolic state, and cell cycle regulation, in comparison to the adverse-risk. Our study provides the first evidence that cellular energetics is transcriptionally deregulated in MDS CD34+ cells and establishes a new useful prognostic score based on the expression of five genes.Juan L. Coelho-SilvaDouglas R. A. SilveiraDiego A. Pereira-MartinsCesar A. O. RojasAntonio R. Lucena-AraujoEduardo M. RegoJoão A. Machado-NetoIsrael BenditVanderson RochaFabiola TrainaNature 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 Juan L. Coelho-Silva Douglas R. A. Silveira Diego A. Pereira-Martins Cesar A. O. Rojas Antonio R. Lucena-Araujo Eduardo M. Rego João A. Machado-Neto Israel Bendit Vanderson Rocha Fabiola Traina Molecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome
description	Abstract Deregulated cellular energetics is formally incorporated as an emerging hallmark of cancer, however little is known about its processes in myelodysplastic syndromes (MDS). Using transcriptomic data of CD34+ cells from 159 MDS patients and 17 healthy donors, we selected 37 genes involved in cellular energetics and interrogated about its clinical and prognostic functions. Based on the low expression of ACLY, ANPEP, and PANK1, as well as high expression of PKM and SLC25A5, we constructed our Molecular-Based Score (MBS), that efficiently discriminated patients at three risks groups: favourable risk (n = 28; 3-year overall survival (OS): 100%); intermediate (n = 60; 76% [62–93%]) and adverse (n = 71; 35% [17–61%]). Adverse MBS risk was independently associated with inferior OS (HR = 10.1 [95% CI 1.26–81]; P = 0.029) in multivariable analysis using age, gender and the revised international prognostic score system as confounders. Transcriptional signature revealed that Favourable- and intermediate-risk patients presented enriched molecular programs related to mature myeloid progenitors, cell cycle progression, and oxidative phosphorylation, indicating that this cells differs in their origin, metabolic state, and cell cycle regulation, in comparison to the adverse-risk. Our study provides the first evidence that cellular energetics is transcriptionally deregulated in MDS CD34+ cells and establishes a new useful prognostic score based on the expression of five genes.
format	article
author	Juan L. Coelho-Silva Douglas R. A. Silveira Diego A. Pereira-Martins Cesar A. O. Rojas Antonio R. Lucena-Araujo Eduardo M. Rego João A. Machado-Neto Israel Bendit Vanderson Rocha Fabiola Traina
author_facet	Juan L. Coelho-Silva Douglas R. A. Silveira Diego A. Pereira-Martins Cesar A. O. Rojas Antonio R. Lucena-Araujo Eduardo M. Rego João A. Machado-Neto Israel Bendit Vanderson Rocha Fabiola Traina
author_sort	Juan L. Coelho-Silva
title	Molecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome
title_short	Molecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome
title_full	Molecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome
title_fullStr	Molecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome
title_full_unstemmed	Molecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome
title_sort	molecular-based score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8ba9e4b1885747c1968531cbed9acd10
work_keys_str_mv	AT juanlcoelhosilva molecularbasedscoreinspiredonmetabolicsignatureimprovesprognosticstratificationformyelodysplasticsyndrome AT douglasrasilveira molecularbasedscoreinspiredonmetabolicsignatureimprovesprognosticstratificationformyelodysplasticsyndrome AT diegoapereiramartins molecularbasedscoreinspiredonmetabolicsignatureimprovesprognosticstratificationformyelodysplasticsyndrome AT cesaraorojas molecularbasedscoreinspiredonmetabolicsignatureimprovesprognosticstratificationformyelodysplasticsyndrome AT antoniorlucenaaraujo molecularbasedscoreinspiredonmetabolicsignatureimprovesprognosticstratificationformyelodysplasticsyndrome AT eduardomrego molecularbasedscoreinspiredonmetabolicsignatureimprovesprognosticstratificationformyelodysplasticsyndrome AT joaoamachadoneto molecularbasedscoreinspiredonmetabolicsignatureimprovesprognosticstratificationformyelodysplasticsyndrome AT israelbendit molecularbasedscoreinspiredonmetabolicsignatureimprovesprognosticstratificationformyelodysplasticsyndrome AT vandersonrocha molecularbasedscoreinspiredonmetabolicsignatureimprovesprognosticstratificationformyelodysplasticsyndrome AT fabiolatraina molecularbasedscoreinspiredonmetabolicsignatureimprovesprognosticstratificationformyelodysplasticsyndrome
_version_	1718387276808978432

Molecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome

Ejemplares similares