{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T10:48:33Z","timestamp":1773398913317,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health-Ricerca Corrente"},{"name":"Ricerca Sanitaria"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2014before any therapy\u2014as 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 \u03b1 chain, clusterin, fibrinogen \u03b3 chain, prothrombin, and vitronectin) were more abundant in the plasma of patients whose HL relapsed (|fold change| \u2265 1.2, p &lt; 0.05, Student\u2019s t-test). Predicting protein function with the Gene Ontology classification model, the proteins were included in four biological processes (p &lt; 0.01). Using immunoblotting and Luminex assays, we validated two of these candidate biomarkers\u2014C4b-binding protein \u03b1 chain and clusterin\u2014linked to innate immune response function (GO:0045087). This study identified C4b-binding protein \u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms23179911","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T01:50:51Z","timestamp":1661997051000},"page":"9911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric\/Adolescent Hodgkin Lymphoma"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0785-5066","authenticated-orcid":false,"given":"Ombretta","family":"Repetto","sequence":"first","affiliation":[{"name":"Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1651-6653","authenticated-orcid":false,"given":"Laura","family":"Caggiari","sequence":"additional","affiliation":[{"name":"Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariangela","family":"De Zorzi","sequence":"additional","affiliation":[{"name":"Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Elia","sequence":"additional","affiliation":[{"name":"AYA Oncology and Pediatric Radiotherapy Unit, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4802-1866","authenticated-orcid":false,"given":"Lara","family":"Mussolin","sequence":"additional","affiliation":[{"name":"Istituto di Ricerca Pediatrica Citt\u00e0 della Speranza, 35127 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Buffardi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, Santobono-Pausilipon Children\u2019s Hospital, 80123 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1190-3198","authenticated-orcid":false,"given":"Marta","family":"Pillon","sequence":"additional","affiliation":[{"name":"Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padova University Hospital, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8813-3200","authenticated-orcid":false,"given":"Paola","family":"Muggeo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, University Hospital of Policlinico, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0087-5355","authenticated-orcid":false,"given":"Tommaso","family":"Casini","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology\/Hematology, Meyer University Children\u2019s Hospital, Via Gaetano Pieraccini 24, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6320-3054","authenticated-orcid":false,"given":"Agostino","family":"Steffan","sequence":"additional","affiliation":[{"name":"Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8205-8665","authenticated-orcid":false,"given":"Christine","family":"Mauz-K\u00f6rholz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Zentrum f\u00fcr Kinderheilkunde der Justus-Liebig-Universit\u00e4t Gie\u00dfen, UKGM Standort Gie\u00dfen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2828-0257","authenticated-orcid":false,"given":"Maurizio","family":"Mascarin","sequence":"additional","affiliation":[{"name":"AYA Oncology and Pediatric Radiotherapy Unit, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6100-9373","authenticated-orcid":false,"given":"Valli","family":"De Re","sequence":"additional","affiliation":[{"name":"Facility of 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