Extracellular Vesicle miR-122-5p as a Prognostic Biomarker in Pediatric Classical Hodgkin Lymphoma
Currently, risk stratification for pediatric Hodgkin lymphoma is based on clinical factors such as stage, bulk, and systemic symptoms. Novel minimally invasive biomarkers could enhance both prognosis and treatment strategies. Therefore, the plasma extracellular vesicles' microRNA profile was characterized by small RNA sequencing in 36 classical Hodgkin lymphoma cases and these findings were confirmed in an extended cohort of 86 patients by RT-qPCR. It was found that the levels of miR-122-5p at diagnosis were significantly higher <i>(p</i>-value: 0.0002) in patients who relapsed compared to patients in remission. The 5-year event-free survival of cases with high and low levels of miR-122-5p was 65 ± 7% and 93 ± 4%, respectively. MiR-122-5p levels were significantly associated with clinical events in both univariate <i>(p</i>-value: 0.0009) and multivariate <i>(p</i>-value: 0.0037) analysis (hazard ratio 5.8). Target prediction analysis suggests an involvement in the polarization of immune cells. The phenotypic characterization of peripheral blood mononuclear cells in 12 patients showed significantly increased levels of CD4+ T-cells in cases with high miR-122-5p levels as compared to low levels <i>(p</i>-value: 0.048). Moreover, CCL17 (TARC) and IL-6 plasma levels at diagnosis were significantly higher as compared to healthy donors <i>(p</i>-value: ≤0.0001). MiR-122-5p could complement current prognostic assays to identify patients at high risk of relapse.
Authors
- Vallì De Re (ORCID: https://orcid.org/0000-0001-6100-9373)
- Egesta Lopci (ORCID: https://orcid.org/0000-0001-9732-1094)
- Alessandra Sala (ORCID: https://orcid.org/0000-0002-6807-9806)
- Anna Garbin
- Lara Mussolin (ORCID: https://orcid.org/0000-0003-4802-1866)
- Elisa Carraro (ORCID: https://orcid.org/0000-0002-6675-867X)
- Stefania Bortoluzzi (ORCID: https://orcid.org/0000-0001-8240-3070)
- Paola Muggeo (ORCID: https://orcid.org/0000-0001-8813-3200)
- Caterina Elia
- Maurizio Mascarin (ORCID: https://orcid.org/0000-0002-2828-0257)
- Marco Pizzi (ORCID: https://orcid.org/0000-0003-4006-7317)
- Marta Pillon (ORCID: https://orcid.org/0000-0002-1190-3198)
- Enrico Gaffo (ORCID: https://orcid.org/0000-0001-6338-7677)
- Gaia Martire (ORCID: https://orcid.org/0009-0007-8161-3632)
- Rebekka J. S. Salzmann (ORCID: https://orcid.org/0000-0002-1032-4848)
- Annalisa Tondo
Institutions
- University of Padua (IT)
- Azienda Ospedaliera San Gerardo (IT)
- Meyer Children's Hospital (IT)
- Centro di Riferimento Oncologico (IT)
- Ospedale Pediatrico Giovanni XXIII (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- IRCCS Humanitas Research Hospital (IT)
- Città della Speranza Foundation (IT)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2024-12-10
- DOI
- https://doi.org/10.3390/ijms252413243
- Citations
- 4
- Primary Topic
- Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.70
Funders
- European Commission
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Associazione Italiana per la Ricerca sul Cancro
- Associazione Italiana Contro le Leucemie-Linfomi e Mieloma
- HORIZON EUROPE Framework Programme
- Agenzia Italiana del Farmaco, Ministero della Salute
- H2020 Marie Skłodowska-Curie Actions