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E-Book 3rd Congress

  • Investigating circRNAs as Prognostic Biomarkers in Acute Myeloid Leukemia (AML); A systematic review and meta-analysis
  • Amir Hossein Aghayan,1,* Yasin Mirazimi,2 Amir Atashi,3 Mohammad Rafiee,4
    1. Student Research Committee, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran
    2. Student Research Committee, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran
    3. Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran.
    4. Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.


  • Introduction: Acute myeloid leukemia (AML) is the predominant subtype of acute leukemia in adults and exhibits significant clinical heterogeneity. The prognosis of AML is intricately influenced by individual-specific factors and disease-specific characteristics. For patients with AML, the selection of appropriate prognostic factors is crucial for predicting disease progression, guiding treatment decisions, and monitoring treatment response. Emerging research has shed light on the potential role of dysregulated circular RNA (circRNA) expression as a promising biomarker in AML prognosis. CircRNAs have diverse functions in intracellular processes such as proliferation, apoptosis, metastasis, and cell cycle regulation, primarily through their interactions with miRNAs and other mechanisms. Due to their impact on survival rates, treatment trends, and their circular structure (which confers high stability in tissues and bodily fluids), circRNAs can be considered novel prognostic biomarkers in AML. Consequently, the present study was conducted to systematically evaluate the prognostic implications of circRNA expression profiles in patients diagnosed with AML.
  • Methods: Original English articles from databases such as PubMed, Scopus, Web of Science, ProQuest, and Google Scholar were searched using different combinations of relevant keywords obtained through MESH from the beginning until March 2023. After extracting the studies from the databases, duplicate studies will be removed. In the next step, screening of the title and abstract of the articles was performed by two authors to determine the relevant studies. Then, the full text of the studies was independently evaluated by two researchers, and the articles were selected based on the inclusion and exclusion criteria. The data collection process was performed based on a checklist predetermined by three authors. The Newcastle-Ottawa Scale (NOS) checklist was used to assess the risk of bias in the included studies. In addition, the certainty of the evidence was assessed using the modified GRADE approach. Also, the hazard ratio (HR) with 95%(CI) was used as the effect size (ES) for performing the prognostic meta-analysis. The I2 statistic was used to determine heterogeneity. In addition, the random effects model (REM) was used to predict the values due to the presence of methodological heterogeneity. Also, to investigate the publication bias, the statistical tests, Egger, Trim and Fill, and Begg were used. Sensitivity analysis was performed using the leave-one-out method. To reduce heterogeneity between studies and find the factor affecting the effect size, subgroup analysis was performed.
  • Results: The study encompassed 1541 patients diagnosed with Acute Myeloid Leukemia (AML), derived from 18 primary research studies. The synthesized findings pertaining to the overall survival (OS) indicator revealed a correlation between dysregulated expression of circular RNAs (circRNAs) and an unfavorable prognosis in AML patients (Hazard Ratio [HR] = 2.05; 95% Confidence Interval [CI]: 1.75 to 2.40). The low I2 value of 15.7% for the OS indicator suggested minimal heterogeneity among the studies. Interpretation areas indicated moderate associations between dysregulated expression of (circRNAs) and AML prognosis , and the GRADE assessment categorized these relationships as moderately certain. Employing the leave-one-out method demonstrated that the exclusion of any individual primary study did not exert a significant impact on the aggregated results. However, an asymmetric distribution in the funnel plot pattern, along with Begg's test (P-value = 0.001) and Egger's test (P-value = 0.005), as well as outcomes from the trim and fill method, collectively signified notable publication bias concerning the OS indicator. Despite conducting an exhaustive search across various databases, our study acknowledges the persistence of publication bias. Language limitations and the possibility of negative results bias, wherein studies with unfavorable outcomes may remain unpublished, contribute to this bias. Subgroup analysis for the OS indicator revealed no substantial disparity in terms of expression status and follow-up time among subgroups. However, it was discerned that studies with a sample size of ≤68 patients tended to overestimate hazard ratio results, emphasizing the importance of opting for a larger sample size to ensure more reliable outcomes.
  • Conclusion: This systematic review and meta-analysis provide evidence that the analysis of circular RNA (circRNA) expression changes can serve as a valuable biomarker for assessing the prognosis of patients with AML. The findings suggest that alterations in circRNA expression profiles can potentially aid in predicting the clinical outcomes of AML patients. Further research and validation studies are warranted to fully establish the clinical utility of circRNA expression as a prognostic biomarker in AML.
  • Keywords: circRNA,Acute myeloid leukemia,prognosis,AML,non-coding RNAs