High expression of IGF2-derived intronic miR-483 predicts outcome in hepatoblastoma.

BACKGROUND: The role of microRNAs (miRs) as biomarkers to predict outcome in hepatoblastoma (HB), the most common malignant liver tumor in childhood, has still to be determined. Recently, the so-called four-miR signature has been described to efficiently stratify HB patients according to their prognosis. OBJECTIVE: We examined the recently described four-miR signature for its clinical relevance in an independent validation cohort of HB patients and tried to optimize its predictive value by analyzing four additional miRs involved in HB biology. METHODS: Expression of eight miR was determined in 29 tumor and 10 normal liver samples by TaqMan assays and association studies and Kaplan-Meier estimators determined their clinical relevance. RESULTS: Stratifying HB patients by the four-miR signature showed no difference in patients' outcome, which was also reflected by the lack of association with any clinical risk parameter. Adding miR-23b-5p and miR-23b-3p did also not increase its discriminating power. However, the integration of miR-483-5p and miR-483-3p into the four-miR signature could predict patients with poor outcome that were associated with large tumors and vessel invasive growth with high accuracy. CONCLUSIONS: The expansion of the four-miR signature by miR-483 serves as a useful biomarker to predict outcome of HB patients.