Abstract
Dysregulation of non-coding microRNAs during the course of tumor development, invasion and/or progression to the distant organs, makes them a promising candidate marker for the diagnosis of cancer and associated malignancies. This exploratory study aims at evaluating the usefulness of plasma concentration of circulating mir-146a as a non-invasive biomarker for acute lymphoblastic leukemia (ALL). Total RNA including miRNA was isolated from 110 plasma samples of patients (n = 66), healthy controls (n = 24) and follow up (n = 20) cases and reverse transcribed. Relative concentrations were assessed using real-time quantitative PCR and fold-change was calculated by 2−ΔΔCt method. Finally, relative concentrations were correlated to clinicopathological factors. Patients (n = 66) were analyzed to determine fold expression of miR-146a in plasma samples of ALL. Before chemotherapy, pediatric (n = 42) and adult (n = 24) showed overexpression of miR-146a compared with healthy controls (P < 0.0001). There was no effect of age and gender on mir-146a expression in plasma. mirR-146a expression was independent of clinical and hematological features. Moreover, miR-146a levels in plasma of paired samples (n = 20) after treatment showed significant decrease in expression (P < 0.001). Expression of plasma miR-146a may be utilized as non-invasive marker to diagnose and predict prognosis in pediatric and adult patients with ALL. Moreover predicted targets may be utilized for ALL therapy in future.
Highlights
Progression to the distant organs, makes them a promising candidate marker for the diagnosis of cancer and associated malignancies
Expression of plasma miR-146a may be utilized as non-invasive marker to diagnose and predict prognosis in pediatric and adult patients with acute lymphoblastic leukemia (ALL)
We concluded that miR-146a up-regulation in plasma may be utilized as a novel, non-invasive marker for diagnosis of ALL in childhood and adults
Summary
Progression to the distant organs, makes them a promising candidate marker for the diagnosis of cancer and associated malignancies This exploratory study aims at evaluating the usefulness of plasma concentration of circulating mir-146a as a non-invasive biomarker for acute lymphoblastic leukemia (ALL). Expression of plasma miR-146a may be utilized as non-invasive marker to diagnose and predict prognosis in pediatric and adult patients with ALL. Current standard methods for diagnosis of ALL have greatly improved diagnosis, but their clinical applications are limited due to their unpleasant, invasive and inconvenient nature It is, of great concern to develop such diagnostic procedures which overcome these limitations including invasive procedures of bone marrow aspiration and biopsy. In developing countries the rate of survival is significantly reduced, possibly due to population differences, poor economic status, late diagnosis, less availability of advanced therapeutics, toxic effects of chemotherapy and most importantly lack of clinical trials on account of diagnosis and prognosis[8]
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