MicroRNA as a prognostic biomarker for survival in childhood acute lymphoblastic leukemia: a systematic review

Recent studies suggest abnormal microRNA (miRNA) expression may have potential prognostic value in childhood acute lymphoblastic leukemia (ALL). In this systematic review, we searched different databases (PubMed, ASH, ASCO, and SIOP) for studies published from 2008 to 2018 that evaluated the prognostic impact of miRNAs in childhood ALL. We also used DIANA-miRPath v3.0 to further characterize the functional role of the significant prognostic miRNAs identified in our systematic review. Here we evaluate 15 studies with a total of 38 different miRNAs and 1545 children with B-cell ALL (B-ALL) or T-cell ALL (T-ALL) recruited over approximately 3 decades (1984-2016) with different treatment protocols and ethnicities. Out of the 15 studies examined, 14 reported 32 dysregulated miRNAs with significant prognostic impact in pediatric ALL patients. Only one Brazilian study reported no significant prognostic effect of 7 miRNAs, while the seventh miRNA (miR-100) showed prognostic significance in a Chinese study. Using DIANA-TarBase v7.0 of DIANA-miRPath v3.0, pathway enrichment analysis revealed 25 miRNAs modulated 24 molecular pathways involved in cancer development. To remove the effect of salvage therapy, 9 studies carried out multivariate cox regression analysis for both relapse-free survival and disease-free survival to develop a panel of 23 miRNAs acting as independent prognostic biomarkers. To enhance the clinical application, utility, and validity of the miRNAs discussed here, their potential prognostic value should be confirmed in larger cohort studies within different ethnicities and different ALL protocols adjusted for other contemporary validated prognostic factors in childhood ALL.