J Cancer 2018; 9(24):4650-4658. doi:10.7150/jca.27560

Research Paper

Proteomic Identification of Plasma Biomarkers in Children and Adolescents with Recurrent Hodgkin Lymphoma

Ombretta Repetto1, Lara Mussolin2, Caterina Elia3, Lia Martina4, Maurizio Bianchi5, Salvatore Buffardi6, Alessandra Sala7, Roberta Burnelli8, Maurizio Mascarin9, Valli De Re10✉

1. Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy;
2. Clinic of Pediatric Haemato-Oncology, Department of Women's and Children's Health, University of Padua, Padua, Institute of Paediatric Research - Fondazione Città della Speranza, Padua, Italy;
3. Pediatric Radioterapy Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy;
4. Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy;
5. Pediatric Onco-Hematology and Stem Cell Transplant Division, City of Health and Science, Regina Margherita Children's Hospital, Turin, Italy;
6. Paediatric Haemato-Oncology department, Santobono-Pausilipon Children's Hospital, Napoli, Italy;
7. Department of Paediatrics, Ospedale San Gerardo, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy;
8. Pediatric Oncology University Hospital, Sant'Anna Hospital, Ferrara, Italy;
9. Pediatric Radioterapy Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy;
10. Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.

Abstract

The treatment of paediatric Hodgkin lymphoma (HL) has steadily improved over the years, so that 10- years survival exceed 80%. The purpose of this study was to identify prognostic markers for relapsed HL that might contribute to optimize therapeutic approaches. To this aim we retrospectively analysed differential protein expression profiles obtained from plasma of children/adolescents with HL (age ranging from 10 to 18 years) collected at diagnosis. We examined the protein profiles of 15 HL relapsed (R) patients compared with 14 HL not relapsed (NR) patients treated with the same LH-2004 protocol. Two dimensional difference in gel electrophoresis (2D-DIGE) revealed significant differences (fold change > 1.5; Student's T-test p<0.01) between R and NR patients in 10 proteins: α-1-antitrypsin chain a, apolipoprotein A-IV precursor; inter-α-trypsin inhibitor heavy chain; antithrombin-III; vitronectin; fibrinogen α, β and γ chains, complement C3, and ceruloplasmin. An up-regulation of fibrinogen α (spots 78, 196, 230, 234, 239) and β (spots 98, 291, 296, 300) chains together with a lower level of α-1-antitrypsin (spots 255, 264, 266, 272, 273) were found in R patients, and this difference was validated by immunoblotting. The functional role(s) of these proteins in the coagulation and inflammation associated with paediatric/adolescent HL progression and relapse deserves further investigations.

Keywords: paediatric Hodgkin lymphoma, DIGE, biomarkers, relapse, plasma proteins

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How to cite this article:
Repetto O, Mussolin L, Elia C, Martina L, Bianchi M, Buffardi S, Sala A, Burnelli R, Mascarin M, De Re V. Proteomic Identification of Plasma Biomarkers in Children and Adolescents with Recurrent Hodgkin Lymphoma. J Cancer 2018; 9(24):4650-4658. doi:10.7150/jca.27560. Available from http://www.jcancer.org/v09p4650.htm