Comparative proteomic profiling in recurrent pediatric/adolescent Hodgkin Lymphoma

O Repetto; L Mussolin; C Elia; L Caggiari; M De Zorzi; A Garbin; C Diamanti; I Gallingani; M Bianchi; S Buffardi; A Sala; R Burnelli; E Facchini; M Mascarin; V De Re

doi:10.1055/s-0040-1701843

Klinische Pädiatrie, Table of Contents

Klin Padiatr 2020; 232(02): 89
DOI: 10.1055/s-0040-1701843

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Comparative proteomic profiling in recurrent pediatric/adolescent Hodgkin Lymphoma

O Repetto

¹Department of Research and Advanced Tumour Diagnostics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, Immunopathology and Tumour Biomarkers Unit/Bio-proteomics Facility, Aviano, Italy

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L Mussolin

²University of Padova, Department of Women’s and Children’s Health, Padova, Italy

³Istituto di Ricerca Pediatrica Città della Speranza, Unit of Onco-hematology, stem cell transplant and gene therapy, Padova, Italy

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C Elia

⁴Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, Pediatric Radioterapy Unit, Padova, Italy

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L Caggiari

¹Department of Research and Advanced Tumour Diagnostics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, Immunopathology and Tumour Biomarkers Unit/Bio-proteomics Facility, Aviano, Italy

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M De Zorzi

¹Department of Research and Advanced Tumour Diagnostics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, Immunopathology and Tumour Biomarkers Unit/Bio-proteomics Facility, Aviano, Italy

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A Garbin

²University of Padova, Department of Women’s and Children’s Health, Padova, Italy

³Istituto di Ricerca Pediatrica Città della Speranza, Unit of Onco-hematology, stem cell transplant and gene therapy, Padova, Italy

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C Diamanti

²University of Padova, Department of Women’s and Children’s Health, Padova, Italy

³Istituto di Ricerca Pediatrica Città della Speranza, Unit of Onco-hematology, stem cell transplant and gene therapy, Padova, Italy

,

I Gallingani

²University of Padova, Department of Women’s and Children’s Health, Padova, Italy

³Istituto di Ricerca Pediatrica Città della Speranza, Unit of Onco-hematology, stem cell transplant and gene therapy, Padova, Italy

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M Bianchi

⁵Regina Margherita Children’s Hospital, Pediatric Onco-Hematology and Stem Cell Transplant Division, City of Health and Science, Torino, Italy

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S Buffardi

⁶Paediatric Haemato-Oncology department, Santobono-Pausilipon Children’s Hospital, Napoli, Italy

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A Sala

⁷Department of Paediatrics, Ospedale San Gerardo, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy

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R Burnelli

⁸Sant’Anna Hospital Pediatric Oncology, Pediatric Oncology University Hospital, Ferrara, Italy

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E Facchini

⁹Department of Pediatrics, University of Bologna, Sant’Orsola-Malpighi Hospital, Bologna, Italy

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M Mascarin

⁴Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, Pediatric Radioterapy Unit, Padova, Italy

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V De Re

¹Department of Research and Advanced Tumour Diagnostics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, Immunopathology and Tumour Biomarkers Unit/Bio-proteomics Facility, Aviano, Italy

› Author Affiliations

Abstract

Full Text

Introduction Inpediatric/adolescent Hodgkin lymphoma (HL) the discovery of protein(s) specifically associated with the presence/absence of relapse may contribute to optimize therapeutic approaches.

Methods Liquid chromatography-mass spectrometry (LC-MS) label-free quantitative proteomics on plasma collected at diagnosis from pediatric/adolescent HL patients was adopted firstly to validate a set of biomarkers predicting disease relapse, and secondly to identify additional candidate protein panels for disease relapse. Protein profiles of 3 not relapsing (NR) HL patients were compared with those of 3 relapsing (R) ones treated with LH-2004 protocol in one ‘explorative’ and two ‘validation’ cohorts.

Results The LC-MS approach validated some differential proteins we previously identified by Differential In Gel Electrophoresis (SERPINC1, SERPINA1, FGB and FGG) [1]. In each protein group belonging to either NR or R patients, bioinformatics functional enrichments showed several biological processes, which were manually grouped into 9 ‘biological classes’. The differential proteins were involved in several biological processes related to either the absence (e.g., regulation of protein metabolism, response and haemostasis) or the presence of relapse (e.g., immune system and cell and extra-cellular matrix architecture). Moreover, additional proteins were found as up-regulated in either NR or R plasma of HL patients, and data were validated with Western Blotting.

Conclusion Overall, our data depict a part of the different molecular scenarios occurring at diagnosis in plasma of HL pediatric/adolescent patients that could affect their different responses to therapy, and provide new evidence about these protein panels as promising biomarkers of relapse in HL pediatric/adolescent disease. Further studies are underway in the EURONET-PHL trial of pediatric/adolescent patients.

References

References
1 Repetto O, Mussolin L, Elia C, Martina L, Bianchi M, Buffardi S, Sala A, Burnelli R, Mascarin M, De Re V. 2018; . Proteomic identification of plasma biomarkers in children and adolescents with recurrent Hodgkin Lymphoma. Journal of Cancer. 9: 4650-4658.