Clinical impact of miR-223 expression in pediatric T-Cell lymphoblastic lymphoma

Abstract

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.