Clinical impact of miR-223 expression in pediatric T-Cell lymphoblastic lymphoma
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Elena Pomari1,2,*, Federica Lovisa1,3,*, Elisa Carraro1, Simona Primerano1,3, Emanuele S.G. D’Amore4, Paolo Bonvini1,3, Luca Lo Nigro5, Rita De Vito6, Luciana Vinti6, Piero Farruggia7, Marta Pillon1, Giuseppe Basso1, Katia Basso8 and Lara Mussolin1,3
1Department of Women’s and Children’s Health, Clinic of Pediatric Hemato-Oncology, University of Padova, 35128 Padova, Italy
2Centre for Tropical Diseases, Ospedale Sacro Cuore-Don Calabria, 37024 Negrar, Italy
3Istituto di Ricerca Pediatrica, Fondazione Città della Speranza, 35127 Padova, Italy
4Institute of Pathology, San Bortolo Hospital, 36100 Vicenza, Italy
5Center of Paediatric Haematology, Azienda Policlinico-OVE, 95123 Catania, Italy
6Department of Paediatric Haemato-Oncology, IRCCS Ospedale Bambino Gesù, 00165 Roma, Italy
7Department of Paediatric Haemato-Oncology, ARNAS Ospedali Civico, G Di Cristina, 90127 Palermo, Italy
8Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, NY 10027, New York, USA
*These authors have contributed equally to this work
Lara Mussolin, email: firstname.lastname@example.org
Keywords: childhood; T-Cell lymphoblastic lymphoma; miR-223
Received: July 12, 2017 Accepted: October 28, 2017 Published: November 11, 2017
Although probability of event-free survival in pediatric lymphoblastic T-cell lymphoma (T-LBL) is about 75%, survival in relapsed patients is very poor, so the identification of new molecular markers is crucial for treatment optimization. Here, we demonstrated that the over-expression of miR-223 promotes tumor T-LBL cell growth, migration and invasion in vitro. We found out that SIK1, an anti-metastatic protein, is a direct target of miR-223 and consequently is significantly reduced in miR-223-overexpressing tumor cells. We measured miR-223 expression levels at diagnosis in tumor biopsies from 67 T-LBL pediatric patients for whom complete clinical and follow up data were available, and we found that high miR-223 expression (above the median value) is associated with worse prognosis (PFS 66% vs 94%, P=0.0036). In addition, the multivariate analysis, conducted taking into account miR-223 expression level and other molecular and clinical characteristics, showed that only high level of miR-223 is an independent factor for worse prognosis. MiR-223 represents a promising marker for treatment stratification in pediatric patients with T-LBL and we provide the first evidence of miR-223 potential role as oncomir by SIK1 repression.
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