Clinical impact of circulating oncogenic MiRNA-221 and MiRNA-222 in glioblastoma multiform

Abstract

Background and aim: Glioblastoma multiform (GBM); most fatal brain cancer, is incurable with molecular diversity hence identification of molecular targets that contribute to GBM tumorgenesis will be suitable for the development of diagnostic and treatment strategies. Micro-RNAs (miR); small RNA molecules, are stable in blood and play a crucial role in molecular processes in GBM. Thus it was aimed to investigate the clinical role of miR-221 and miR-222 among GBM cases as compared to healthy individuals and illustrate their role in patient’s survival. Materials and methods: Blood samples were withdrawn from 20 GBM cases before and after treatment, a group of 20 healthy individuals were served as control. For all enrolled samples expression of miR-221 and miR-222 were detected using quantitative PCR (QPCR). Sensitivities, specificities of investigated miRs and their relation with GBM clinical characteristics and patient’s outcome were analyzed using Kaplan Meir curve. Results: Expression of investigated miR- 221 and -222 were significantly increased in GBM cases as compared to healthy individuals (F = 12.9, at P < 0.001, F = 28.78, at P < 0.0001, respectively) and with absolute specificity for both and 90% sensitivity for miR-221 and 85% for miR-222. Among GBM patients (n = 20), mean expression level miR-221 reported significant increase with elder GBM (> 60 years) at F = 5.7, P = 0.028, while both miR-221 and -222 showed significant difference in performance status (ECGO) at P = 0.036 and 0.007, patients with primary lesion at P = 0.001 and 0.005, surgically treatment strategy at P < 0.001 and 0.004, respectively. Patients were grouped according to their outcomes into response (complete [CR] or partial [PR]), stable disease[SD] and progressive disease [PD], miR-221 and miR-222 showed increase expression with PD and patients with worse PFS and OS were those with high miRs expression. Conclusion: Detection of circulating miR-221 and miR-222 may be used as circulating molecular marker for diagnosis and prediction of outcome for patients with GBM. Further studies with large cohort of samples are encouraged.