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Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

The identification of circulating proteins associated with relapse in pediatric Hodgkin lymphoma (HL) may help develop predictive biomarkers. We previously identified a set of predictive biomarkers by difference gel electrophoresis. Here we used label-free quantitative liquid chromatography-mass spe...

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Autores principales: Repetto, Ombretta, De Re, Valli, Mussolin, Lara, Tedeschi, Massimo, Elia, Caterina, Bianchi, Maurizio, Buffardi, Salvatore, Sala, Alessandra, Burnelli, Roberta, Mascarin, Maurizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139997/
https://www.ncbi.nlm.nih.gov/pubmed/32235718
http://dx.doi.org/10.3390/ijms21062185
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author Repetto, Ombretta
De Re, Valli
Mussolin, Lara
Tedeschi, Massimo
Elia, Caterina
Bianchi, Maurizio
Buffardi, Salvatore
Sala, Alessandra
Burnelli, Roberta
Mascarin, Maurizio
author_facet Repetto, Ombretta
De Re, Valli
Mussolin, Lara
Tedeschi, Massimo
Elia, Caterina
Bianchi, Maurizio
Buffardi, Salvatore
Sala, Alessandra
Burnelli, Roberta
Mascarin, Maurizio
author_sort Repetto, Ombretta
collection PubMed
description The identification of circulating proteins associated with relapse in pediatric Hodgkin lymphoma (HL) may help develop predictive biomarkers. We previously identified a set of predictive biomarkers by difference gel electrophoresis. Here we used label-free quantitative liquid chromatography-mass spectrometry (LC-MS/MS) on plasma collected at diagnosis from 12 children (age 12–16 years) with nodular sclerosis HL, including six in whom the disease relapsed within 5 years of treatment in the LH2004 trial. Plasma proteins were pooled in groups of three, separately for non-relapsing and relapsing HL, and differentially abundant proteins between the two disease states were identified by LC-MS/MS in an explorative and validation design. Proteins with a fold change in abundance >1.2 or ≤0.8 were considered “differentially abundant”. LC-MS/MS identified 60 and 32 proteins that were more abundant in non-relapsing and relapsing HL plasma, respectively, in the explorative phase; these numbers were 39 and 34 in the validation phase. In both analyses, 11 proteins were more abundant in non-relapsing HL (e.g., angiotensinogen, serum paraoxonase/arylesterase 1, transthyretin), including two previously identified by difference gel electrophoresis (antithrombin III and α-1-antitrypsin); seven proteins were more abundant in relapsing HL (e.g., fibronectin and thrombospondin-1), including two previously identified proteins (fibrinogen β and γ chains). The differentially abundant proteins participated in numerous biological processes, which were manually grouped into 10 biological classes and 11 biological regulatory subclasses. The biological class Lipid metabolism, and its regulatory subclass, included angiotensinogen and serum paraoxonase/arylesterase 1 (more abundant in non-relapsing HL). The biological classes Immune system and Cell and extracellular matrix architecture included fibronectin and thrombospondin-1 (more abundant in relapsing HL). These findings deepen our understanding of the molecular scenario underlying responses to therapy and provide new evidence about these proteins as possible biomarkers of relapse in pediatric HL.
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spelling pubmed-71399972020-04-13 Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma Repetto, Ombretta De Re, Valli Mussolin, Lara Tedeschi, Massimo Elia, Caterina Bianchi, Maurizio Buffardi, Salvatore Sala, Alessandra Burnelli, Roberta Mascarin, Maurizio Int J Mol Sci Article The identification of circulating proteins associated with relapse in pediatric Hodgkin lymphoma (HL) may help develop predictive biomarkers. We previously identified a set of predictive biomarkers by difference gel electrophoresis. Here we used label-free quantitative liquid chromatography-mass spectrometry (LC-MS/MS) on plasma collected at diagnosis from 12 children (age 12–16 years) with nodular sclerosis HL, including six in whom the disease relapsed within 5 years of treatment in the LH2004 trial. Plasma proteins were pooled in groups of three, separately for non-relapsing and relapsing HL, and differentially abundant proteins between the two disease states were identified by LC-MS/MS in an explorative and validation design. Proteins with a fold change in abundance >1.2 or ≤0.8 were considered “differentially abundant”. LC-MS/MS identified 60 and 32 proteins that were more abundant in non-relapsing and relapsing HL plasma, respectively, in the explorative phase; these numbers were 39 and 34 in the validation phase. In both analyses, 11 proteins were more abundant in non-relapsing HL (e.g., angiotensinogen, serum paraoxonase/arylesterase 1, transthyretin), including two previously identified by difference gel electrophoresis (antithrombin III and α-1-antitrypsin); seven proteins were more abundant in relapsing HL (e.g., fibronectin and thrombospondin-1), including two previously identified proteins (fibrinogen β and γ chains). The differentially abundant proteins participated in numerous biological processes, which were manually grouped into 10 biological classes and 11 biological regulatory subclasses. The biological class Lipid metabolism, and its regulatory subclass, included angiotensinogen and serum paraoxonase/arylesterase 1 (more abundant in non-relapsing HL). The biological classes Immune system and Cell and extracellular matrix architecture included fibronectin and thrombospondin-1 (more abundant in relapsing HL). These findings deepen our understanding of the molecular scenario underlying responses to therapy and provide new evidence about these proteins as possible biomarkers of relapse in pediatric HL. MDPI 2020-03-22 /pmc/articles/PMC7139997/ /pubmed/32235718 http://dx.doi.org/10.3390/ijms21062185 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Repetto, Ombretta
De Re, Valli
Mussolin, Lara
Tedeschi, Massimo
Elia, Caterina
Bianchi, Maurizio
Buffardi, Salvatore
Sala, Alessandra
Burnelli, Roberta
Mascarin, Maurizio
Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma
title Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma
title_full Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma
title_fullStr Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma
title_full_unstemmed Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma
title_short Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma
title_sort proteomic profiles and biological processes of relapsed vs. non-relapsed pediatric hodgkin lymphoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139997/
https://www.ncbi.nlm.nih.gov/pubmed/32235718
http://dx.doi.org/10.3390/ijms21062185
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