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Open AccessArticle

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

1
Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico (CRO) di Aviano, IRCCS, 33081 Aviano (PN), Italy
2
Clinic of Pediatric Haemato-Oncology, Department of Women’s and Children’s Health, Institute of Paediatric Research—Fondazione Città della Speranza, University of Padua, 35122 Padua, Italy
3
Pediatric Radiotherapy Unit, Centro di Riferimento Oncologico (CRO) di Aviano, IRCCS, 33081 Aviano (PN), Italy
4
Pediatric Onco-Hematology and Stem Cell Transplant Division, City of Health and Science, Regina Margherita Children’s Hospital, 10126 Turin, Italy
5
Paediatric Haemato-Oncology Department, Santobono-Pausilipon Children’s Hospital, 80129 Naples, Italy
6
Department of Paediatrics, Ospedale San Gerardo, University of Milano-Bicocca, Fondazione MBBM, 20052 Monza, Italy
7
Pediatric Oncology University Hospital, Sant’Anna Hospital, 44124 Ferrara, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(6), 2185; https://doi.org/10.3390/ijms21062185
Received: 5 March 2020 / Accepted: 19 March 2020 / Published: 22 March 2020
(This article belongs to the Section Biochemistry)
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. View Full-Text
Keywords: biomarker; cancer; label-free quantification; pediatric Hodgkin lymphoma; plasma; protein mass spectrometry; proteomics; relapse biomarker; cancer; label-free quantification; pediatric Hodgkin lymphoma; plasma; protein mass spectrometry; proteomics; relapse
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MDPI and ACS Style

Repetto, O.; De Re, V.; Mussolin, L.; Tedeschi, M.; Elia, C.; Bianchi, M.; Buffardi, S.; Sala, A.; Burnelli, R.; Mascarin, M. Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma. Int. J. Mol. Sci. 2020, 21, 2185.

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