Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric/Adolescent Hodgkin Lymphoma
Classical pediatric Hodgkin Lymphoma (HL) is a rare malignancy. Therapeutic regimens for its management may be optimized by establishing treatment response early on. The aim of this study was to identify plasma protein biomarkers enabling the prediction of relapse in pediatric/adolescent HL patients...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/17/9911 |
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| author | Ombretta Repetto Laura Caggiari Mariangela De Zorzi Caterina Elia Lara Mussolin Salvatore Buffardi Marta Pillon Paola Muggeo Tommaso Casini Agostino Steffan Christine Mauz-Körholz Maurizio Mascarin Valli De Re |
| author_facet | Ombretta Repetto Laura Caggiari Mariangela De Zorzi Caterina Elia Lara Mussolin Salvatore Buffardi Marta Pillon Paola Muggeo Tommaso Casini Agostino Steffan Christine Mauz-Körholz Maurizio Mascarin Valli De Re |
| author_sort | Ombretta Repetto |
| collection | DOAJ |
| description | Classical pediatric Hodgkin Lymphoma (HL) is a rare malignancy. Therapeutic regimens for its management may be optimized by establishing treatment response early on. The aim of this study was to identify plasma protein biomarkers enabling the prediction of relapse in pediatric/adolescent HL patients treated under the pediatric EuroNet-PHL-C2 trial. We used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics at the time of diagnosis—before any therapy—as semiquantitative method to profile plasma proteins specifically associated with relapse in 42 children with nodular sclerosing HL. In both the exploratory and the validation cohorts, six proteins (apolipoprotein E, C4b-binding protein α chain, clusterin, fibrinogen γ chain, prothrombin, and vitronectin) were more abundant in the plasma of patients whose HL relapsed (|fold change| ≥ 1.2, <i>p</i> < 0.05, Student’s <i>t</i>-test). Predicting protein function with the Gene Ontology classification model, the proteins were included in four biological processes (<i>p</i> < 0.01). Using immunoblotting and Luminex assays, we validated two of these candidate biomarkers—C4b-binding protein α chain and clusterin—linked to innate immune response function (GO:0045087). This study identified C4b-binding protein α chain and clusterin as candidate early plasma biomarkers of HL relapse, and important for the purpose of shedding light on the molecular scenario associated with immune response in patients treated under the EuroNet-PHL-C2 trial. |
| first_indexed | 2024-03-10T01:42:54Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:42:54Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-07478dd0b1da4fb89b631d282e6528632023-11-23T13:19:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012317991110.3390/ijms23179911Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric/Adolescent Hodgkin LymphomaOmbretta Repetto0Laura Caggiari1Mariangela De Zorzi2Caterina Elia3Lara Mussolin4Salvatore Buffardi5Marta Pillon6Paola Muggeo7Tommaso Casini8Agostino Steffan9Christine Mauz-Körholz10Maurizio Mascarin11Valli De Re12Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, ItalyFacility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, ItalyFacility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, ItalyAYA Oncology and Pediatric Radiotherapy Unit, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, ItalyIstituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, ItalyDepartment of Pediatric Hemato-Oncology, Santobono-Pausilipon Children’s Hospital, 80123 Napoli, ItalyPediatric Hematology, Oncology and Stem Cell Transplant Division, Padova University Hospital, 35128 Padova, ItalyDepartment of Pediatric Hemato-Oncology, University Hospital of Policlinico, 70124 Bari, ItalyDivision of Pediatric Oncology/Hematology, Meyer University Children’s Hospital, Via Gaetano Pieraccini 24, 50139 Florence, ItalyFacility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, ItalyDepartment of Pediatric Oncology, Zentrum für Kinderheilkunde der Justus-Liebig-Universität Gießen, UKGM Standort Gießen, 35392 Giessen, GermanyAYA Oncology and Pediatric Radiotherapy Unit, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, ItalyFacility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, ItalyClassical pediatric Hodgkin Lymphoma (HL) is a rare malignancy. Therapeutic regimens for its management may be optimized by establishing treatment response early on. The aim of this study was to identify plasma protein biomarkers enabling the prediction of relapse in pediatric/adolescent HL patients treated under the pediatric EuroNet-PHL-C2 trial. We used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics at the time of diagnosis—before any therapy—as semiquantitative method to profile plasma proteins specifically associated with relapse in 42 children with nodular sclerosing HL. In both the exploratory and the validation cohorts, six proteins (apolipoprotein E, C4b-binding protein α chain, clusterin, fibrinogen γ chain, prothrombin, and vitronectin) were more abundant in the plasma of patients whose HL relapsed (|fold change| ≥ 1.2, <i>p</i> < 0.05, Student’s <i>t</i>-test). Predicting protein function with the Gene Ontology classification model, the proteins were included in four biological processes (<i>p</i> < 0.01). Using immunoblotting and Luminex assays, we validated two of these candidate biomarkers—C4b-binding protein α chain and clusterin—linked to innate immune response function (GO:0045087). This study identified C4b-binding protein α chain and clusterin as candidate early plasma biomarkers of HL relapse, and important for the purpose of shedding light on the molecular scenario associated with immune response in patients treated under the EuroNet-PHL-C2 trial.https://www.mdpi.com/1422-0067/23/17/9911biomarkerlabel-free quantificationmass spectrometrypediatric Hodgkin Lymphomaproteomicsrelapse |
| spellingShingle | Ombretta Repetto Laura Caggiari Mariangela De Zorzi Caterina Elia Lara Mussolin Salvatore Buffardi Marta Pillon Paola Muggeo Tommaso Casini Agostino Steffan Christine Mauz-Körholz Maurizio Mascarin Valli De Re Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric/Adolescent Hodgkin Lymphoma International Journal of Molecular Sciences biomarker label-free quantification mass spectrometry pediatric Hodgkin Lymphoma proteomics relapse |
| title | Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric/Adolescent Hodgkin Lymphoma |
| title_full | Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric/Adolescent Hodgkin Lymphoma |
| title_fullStr | Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric/Adolescent Hodgkin Lymphoma |
| title_full_unstemmed | Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric/Adolescent Hodgkin Lymphoma |
| title_short | Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric/Adolescent Hodgkin Lymphoma |
| title_sort | quantitative plasma proteomics to identify candidate biomarkers of relapse in pediatric adolescent hodgkin lymphoma |
| topic | biomarker label-free quantification mass spectrometry pediatric Hodgkin Lymphoma proteomics relapse |
| url | https://www.mdpi.com/1422-0067/23/17/9911 |
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