• miR-181a and miR-155 as Prognostic Biomarkers in Pediatric ALL: A Bioinformatic Insight
  • Mohamadamir kakaee,1,*
    1. shahid beheshti university of medical sciences


  • Introduction: Pediatric acute lymphoblastic leukemia (ALL) is the most common cancer in children. Despite high cure rates, a subset of patients experience relapse and poor outcomes. MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have emerged as potential biomarkers in various cancers, including ALL. This study aimed to identify prognostic miRNA signatures associated with overall survival in pediatric ALL using bioinformatics analysis of publicly available datasets
  • Methods: MiRNA expression data and corresponding clinical survival information for pediatric ALL patients (n = 93) were retrieved from the TARGET (Therapeutically Applicable Research to Generate Effective Treatments) initiative, a comprehensive resource for pediatric cancer genomics. The raw miRNA count data underwent quality control, normalization, and log2 transformation to ensure comparability across samples. Patients were categorized into two groups based on survival status at the last follow-up: those who were alive versus those who were deceased. Differential expression analysis was then performed between these two groups using statistical thresholds of adjusted p-value < 0.05 and absolute log2 fold change > 1 (equivalent to fold-change > 2) to identify significantly dysregulated miRNAs. A volcano plot was generated to visualize the distribution of miRNAs based on statistical significance and fold change. To further explore the clinical relevance of identified miRNAs, Kaplan-Meier survival curves were constructed for each candidate miRNA using the Lifelines package in Python, and log-rank tests were employed to assess the statistical significance of differences in survival between high- and low-expression groups. Additionally, a heatmap was created to display the expression profiles of the top 10 differentially expressed miRNAs across all samples using Seaborn.
  • Results: The analysis identified ten miRNAs that were significantly dysregulated between patients with favorable versus unfavorable survival outcomes. Among these, miR-181a and miR-155 emerged as the most promising prognostic biomarkers. MiR-181a showed significantly higher expression levels in patients with poor survival, with a log2 fold change > 1.5 and an adjusted p-value < 0.01. Kaplan-Meier analysis demonstrated that patients with high miR-181a expression had markedly reduced overall survival compared to those with low expression levels (p = 0.002). This suggests that miR-181a may function as an oncogenic miRNA contributing to disease aggressiveness or therapy resistance. In contrast, miR-155 was upregulated in patients with better survival outcomes and showed a moderate but statistically significant association with improved overall survival (p = 0.049). The volcano plot clearly highlighted the opposing trends of these two miRNAs, with miR-181a in the upregulated cluster for poor survival and miR-155 in the favorable cluster. The heatmap analysis provided further evidence of distinct expression signatures, with consistent patterns of elevated miR-181a and reduced miR-155 in high-risk patients. Other notable miRNAs in the top ten list included miR-99a, miR-130b, miR-146b, and miR-29c, some of which have been previously implicated in leukemogenesis or immune regulation.
  • Conclusion: In summary, this bioinformatics-based analysis of pediatric ALL patients from the TARGET dataset identified a set of prognostically relevant miRNAs, with miR-181a and miR-155 demonstrating the strongest associations with overall survival. High expression of miR-181a was linked to significantly worse prognosis, while increased levels of miR-155 were associated with improved outcomes. These findings underscore the potential of miRNAs as prognostic biomarkers in pediatric ALL and highlight the value of integrating genomic and clinical data to uncover novel targets for risk stratification and precision medicine. While these results are promising, further validation studies in larger and independent cohorts are necessary to confirm their clinical applicability and to explore the underlying biological mechanisms driving these associations
  • Keywords: microRNA, miR-181a, miR-155, prognosis, TARGET