The Significance of miRNAs as a Prognostic Biomarker for Survival Outcome in T Cell – Acute Lymphoblastic Leukemia Patients: A Systematic Review and Meta-Analysis
Received 7 January 2019
Accepted for publication 11 April 2019
Published 5 February 2020 Volume 2020:12 Pages 819—839
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Kenan Onel
Shanthi Sabarimurugan, 1 Chellan Kumarasamy, 2 Madurantakam Royam Madhav, 3 Suja Samiappan, 4 Rama Jayaraj 5
1Theranostics, GenesisCare, Perth, WA, Australia; 2University of Adelaide, North Terrace Campus, Adelaide, SA 5005, Australia; 3School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India 632014; 4Department of Biochemistry, Bharathiar University, Coimbatore, Tamil Nadu, India; 5Clinical Sciences, College of Health and Human Sciences, Charles Darwin University, Darwin, Northern Territory 0909, Australia
Correspondence: Rama Jayaraj
Clinical Sciences, College of Health and Human Sciences, Charles Darwin University, Ellengowan Drive, Darwin, Northern Territory 0909, Australia
Purpose: T-cell acute lymphoblastic leukemia (T-ALL) affects lymphoid cells. Previous studies have reported that miRNAs play a significant role in T-ALL prognosis and have the potential to function as biomarkers in T-ALL. Therefore, this systematic review and meta-analysis study was designed to evaluate the overall prognostic impact of miRNAs in T-ALL patients.
Methods: Eligible studies published between Jan 2010 and April 2018 were retrieved from online bibliographic databases based on multiple keywords to generate search strings. Meta-analysis was performed using the outcome measure, Hazard Ratio (HR). A survival analysis of all studies was conducted and a subsequent forest plot was generated to evaluate the pooled effect size, across all T-ALL patients. Subgroup analysis was conducted based on demographic characteristics and commonly represented miRNAs among the included studies.
Results: A total of 17 studies were included for systematic review, among which 16 studies were eligible for meta-analysis, which, in total discussed 32 different miRNAs. The mean effect size of HR value was 0.929 (CI 0.878– 0984), which indicates a decrease in risk of death by 7.1%. The analysis was based on the random effects model with the heterogeneity measure index (I 2) being 84.92%. The pooled effect size (HR) of upregulated and downregulated miRNA expressions on survival outcome in the T-ALL patient was 0.787 (CI 0.732– 0.845) and 1.225 (CI 1.110– 1.344) respectively. The subgroup analysis was performed based on demographic characteristics (age, gender, lactate dehydrogenase, WBC count) and expression of miR221 and miR46a.
Conclusion: Our systematic review and meta-analysis findings suggest that the overall miRNA expression is potentially associated with a decreased likelihood of death in T-ALL patients. Although our findings are inconclusive, the results point toward miRNA expression allowing for prognostic evaluation of T-ALL patients.
Keywords: microRNAs, prognosis, biomarkers, survival analysis, PRISMA
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