Potential biomarkers of Ewing sarcoma identified through a Europe-wide analysis of prospectively collected samples.

Clinical features, aside from disease stage, have proven insufficient to identify patients at extremely high or low risk. There are few established biological markers for EwS. The discovery of new prognostic and/or predictive biomarkers could improve our understanding of tumor heterogeneity, facilit...

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Autores: Ranft A, Richter GHS, Diaz-Martin J, Jabar S, Jens M, Kerkhoff M, Blanquer-Maceiras M, Noguera R, Piro I, Steiger K, Burdach S, Parra A, Picci P, Gambarotti M, Hartmann W, Scotlandi K, de Alava E, Dirksen U
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:dnet:incliva_____::bd4677aa8d19a1d362d982820fdbab3e
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/20863
Access Level:acceso abierto
Palabra clave:Biomarkers
Ewing sarcoma
Prognosis
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spelling Potential biomarkers of Ewing sarcoma identified through a Europe-wide analysis of prospectively collected samples.Ranft ARichter GHSDiaz-Martin JJabar SJens MKerkhoff MBlanquer-Maceiras MNoguera RPiro ISteiger KBurdach SParra APicci PGambarotti MHartmann WScotlandi Kde Alava EDirksen UBiomarkersEwing sarcomaPrognosisClinical features, aside from disease stage, have proven insufficient to identify patients at extremely high or low risk. There are few established biological markers for EwS. The discovery of new prognostic and/or predictive biomarkers could improve our understanding of tumor heterogeneity, facilitate individual risk stratification, and aid targeted therapies. We initiated a pan-European study using formalin-fixed, prospectively collected, primary tumors prior to chemotherapy from 335 patients in two clinical trial registries, EURO-Ewing 99 and Ewing 2008, to analyze correlation and survival of ten potential prognostic biomarkers. Immunohistochemical (IHC) analyses were conducted for STEAP1, DKK2, and EZH2, while MIR34A and LGALS3BP expression was investigated by quantitative PCR. Genomic alterations, including gain of chromosome 1q, loss of ADAM3A, loss of chromosome 16q, as well as loss of heterozygosity (LOH) and percentage of the genome altered (PGA), were analyzed by FISH and/or SNP-based arrays of genomic DNA. To consider the observed variation in the number of analyzed samples per biomarker (N = 102-300), effect size measures were computed. Correlations between dichotomized biomarker expressions were generally low, except for those reflecting genomic alterations (phi >= 0.20 <= 0.38; P < .05). Several relevant correlations were found with clinical features of the underlying EwS patients (phi >= 0.20 <= 0.31; P < .05). Most promising prognostic values with clinically relevant effect sizes (OS), adjusted for known prognostic variables, were high MIR34A expression (HR = 0.29; P < .01), LOH (HR = 2.44; P < .05), and PGA (HR = 2.20; P = .05). This pan-European study identified MIR34A, LOH, and PGA as the most promising biomarkers for the prognosis of survival in a well-characterized EWS patient cohort.NATURE PORTFOLIO2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/20863Scientific ReportsISSN: 20452322reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:dnet:incliva_____::bd4677aa8d19a1d362d982820fdbab3e2026-06-07T16:35:31Z
dc.title.none.fl_str_mv Potential biomarkers of Ewing sarcoma identified through a Europe-wide analysis of prospectively collected samples.
title Potential biomarkers of Ewing sarcoma identified through a Europe-wide analysis of prospectively collected samples.
spellingShingle Potential biomarkers of Ewing sarcoma identified through a Europe-wide analysis of prospectively collected samples.
Ranft A
Biomarkers
Ewing sarcoma
Prognosis
title_short Potential biomarkers of Ewing sarcoma identified through a Europe-wide analysis of prospectively collected samples.
title_full Potential biomarkers of Ewing sarcoma identified through a Europe-wide analysis of prospectively collected samples.
title_fullStr Potential biomarkers of Ewing sarcoma identified through a Europe-wide analysis of prospectively collected samples.
title_full_unstemmed Potential biomarkers of Ewing sarcoma identified through a Europe-wide analysis of prospectively collected samples.
title_sort Potential biomarkers of Ewing sarcoma identified through a Europe-wide analysis of prospectively collected samples.
dc.creator.none.fl_str_mv Ranft A
Richter GHS
Diaz-Martin J
Jabar S
Jens M
Kerkhoff M
Blanquer-Maceiras M
Noguera R
Piro I
Steiger K
Burdach S
Parra A
Picci P
Gambarotti M
Hartmann W
Scotlandi K
de Alava E
Dirksen U
author Ranft A
author_facet Ranft A
Richter GHS
Diaz-Martin J
Jabar S
Jens M
Kerkhoff M
Blanquer-Maceiras M
Noguera R
Piro I
Steiger K
Burdach S
Parra A
Picci P
Gambarotti M
Hartmann W
Scotlandi K
de Alava E
Dirksen U
author_role author
author2 Richter GHS
Diaz-Martin J
Jabar S
Jens M
Kerkhoff M
Blanquer-Maceiras M
Noguera R
Piro I
Steiger K
Burdach S
Parra A
Picci P
Gambarotti M
Hartmann W
Scotlandi K
de Alava E
Dirksen U
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biomarkers
Ewing sarcoma
Prognosis
topic Biomarkers
Ewing sarcoma
Prognosis
description Clinical features, aside from disease stage, have proven insufficient to identify patients at extremely high or low risk. There are few established biological markers for EwS. The discovery of new prognostic and/or predictive biomarkers could improve our understanding of tumor heterogeneity, facilitate individual risk stratification, and aid targeted therapies. We initiated a pan-European study using formalin-fixed, prospectively collected, primary tumors prior to chemotherapy from 335 patients in two clinical trial registries, EURO-Ewing 99 and Ewing 2008, to analyze correlation and survival of ten potential prognostic biomarkers. Immunohistochemical (IHC) analyses were conducted for STEAP1, DKK2, and EZH2, while MIR34A and LGALS3BP expression was investigated by quantitative PCR. Genomic alterations, including gain of chromosome 1q, loss of ADAM3A, loss of chromosome 16q, as well as loss of heterozygosity (LOH) and percentage of the genome altered (PGA), were analyzed by FISH and/or SNP-based arrays of genomic DNA. To consider the observed variation in the number of analyzed samples per biomarker (N = 102-300), effect size measures were computed. Correlations between dichotomized biomarker expressions were generally low, except for those reflecting genomic alterations (phi >= 0.20 <= 0.38; P < .05). Several relevant correlations were found with clinical features of the underlying EwS patients (phi >= 0.20 <= 0.31; P < .05). Most promising prognostic values with clinically relevant effect sizes (OS), adjusted for known prognostic variables, were high MIR34A expression (HR = 0.29; P < .01), LOH (HR = 2.44; P < .05), and PGA (HR = 2.20; P = .05). This pan-European study identified MIR34A, LOH, and PGA as the most promising biomarkers for the prognosis of survival in a well-characterized EWS patient cohort.
publishDate 2026
dc.date.none.fl_str_mv 2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/20863
url https://incliva.portalinvestigacion.com/publicaciones/20863
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv NATURE PORTFOLIO
publisher.none.fl_str_mv NATURE PORTFOLIO
dc.source.none.fl_str_mv Scientific Reports
ISSN: 20452322
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
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