Clinical Trials Unit, Clinical Research, Children's Cancer Hospital Egypt-57357 (CCHE-57357), Cairo, Egypt.
Biostatistics Unit, Clinical Research, Children's Cancer Hospital Egypt-57357 (CCHE-57357), Cairo, Egypt.
Cancer Metastasis Rev. 2019 Dec;38(4):771-782. doi: 10.1007/s10555-019-09826-0.
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.
最近的研究表明，异常的 microRNA（miRNA）表达可能在儿童急性淋巴细胞白血病（ALL）中有潜在的预后价值。在这项系统综述中，我们搜索了不同的数据库（PubMed、ASH、ASCO 和 SIOP），以评估 2008 年至 2018 年间发表的评估 miRNA 在儿童 ALL 中预后影响的研究。我们还使用 DIANA-miRPath v3.0 进一步分析我们系统综述中确定的有显著预后意义的 miRNA 的功能作用。在这里，我们评估了 15 项研究，共涉及 38 种不同的 miRNA 和 1545 名患有 B 细胞 ALL（B-ALL）或 T 细胞 ALL（T-ALL）的儿童，这些儿童是在大约 30 年的时间内（1984-2016 年），采用不同的治疗方案和种族招募的。在检查的 15 项研究中，有 14 项报告了 32 种失调的 miRNA，这些 miRNA 在儿科 ALL 患者中有显著的预后影响。只有一项巴西研究报告 7 种 miRNA 没有显著的预后作用，而第七种 miRNA（miR-100）在中国的一项研究中显示出了预后意义。使用 DIANA-miRPath v3.0 的 DIANA-TarBase v7.0，通路富集分析显示，25 种 miRNA 调节了涉及癌症发展的 24 种分子通路。为了去除挽救治疗的影响，9 项研究进行了多变量 cox 回归分析，以评估无复发生存率和无病生存率，并开发了一组 23 种 miRNA，作为独立的预后生物标志物。为了增强这里讨论的 miRNA 的临床应用、实用性和有效性，应该在不同种族和不同 ALL 方案中进行更大规模的队列研究，以确认其潜在的预后价值，并针对儿童 ALL 中的其他当代验证预后因素进行调整。
