Introduction Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, characterized by disruptions in the differentiation and proliferation of lymphoid progenitor cells (۱, ۲). Prognostic biomarkers are essential to guide treatment strategies and improve patient outcomes. MicroRNAs, as small non-coding RNAs, are involved in post-transcriptional gene expression regulation of ۳۰% of genes by binding to ۳′ untranslated region (UTR) of mRNAs (۳, ۴). Recent research has identified microRNAs (miRNAs) as crucial post-transcriptional regulators of gene expression involved in various cancer-related pathways (۵-۷). However, the predictive value of specific miRNAs in ALL
prognosis remains unclear. This systematic review and meta-analysis aims to evaluate the role of miRNAs as prognostic biomarkers in ALL, focusing on their potential to predict outcomes. Materials and Method A comprehensive literature search was conducted using PubMed, Web of Science, Scopus, and EMBASE databases up to April ۲۰۲۴. Out of ۸۵۶ results, studies investigating the association of miRNA expression with survival outcomes in ALL patients were included. Two independent reviewers screened eligible studies, and data were extracted regarding country, study design, age, sample origin, miRNA expression cut-off, miRNA profiling techniques, and prognostic outcomes, including hazard ratios (HR) with ۹۵% confidence intervals (CIs). The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using a random-effects model to calculate pooled HRs with ۹۵% CIs for OS and RFS based on miRNA expression levels (Fig. ۱). Heterogeneity was assessed using the I² statistic, and publication bias was evaluated through funnel plot analysis (Fig. ۲). Result Twenty-one studies (۱۹۰۰ patients) were included, of which ۲۴ miRNAs were reported to be up-regulated, and ۱۷ were mentioned to be down-regulated. No significant publication bias was detected. miRNAs can indicate both improved or poorer survival, which is measured by different outcomes, such as OS, DFS, EFS, etc. Besides, three miRs were found to be protective for ALL prognoses based on more than one population. High expression of mir۱۲۵b, miR-۳۳۵, and miR-۲۱۰ correlates with improved survival (pooled HR: ۰.۳۱ (۰.۲۲-۰.۴۴); HR: ۰.۲۹ (۰.۱۲–۰.۶۸); HR: ۰.۲۲ (۰.۰۶–۰.۸۴); respectively). Conclusion This systematic review and meta-analysis show that specific miRNAs, particularly miR-۱۲۵b, miR-۳۳۵, and miR-۲۱۰, have significant prognostic value in ALL. These findings suggest that miRNAs could serve as non-invasive biomarkers to stratify patients based on risk, thereby enabling more personalized treatment approaches. Additionally, further studies for specific miRs are needed to fully elucidate the prognostic utility of miRNAs across different age groups.