Genetic Engineering and Biotechnology Research Division, Biochemistry Department, National Research Centre, Dokki, Giza, Egypt.
High Throughput Molecular and Genetic Laboratory, Center for Excellences for Advanced Sciences, National Research Centre, El-Bohouth Street, Dokki, Giza, 12622, Egypt.
J Neurooncol. 2019 Sep;144(3):545-551. doi: 10.1007/s11060-019-03256-2. Epub 2019 Aug 17.
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.
Blood samples were withdrawn from 20 GBM cases before and after treatment, a group of 20 healthy individuals were served as control.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.
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.
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.
多形性胶质母细胞瘤（GBM）是最致命的脑癌，由于分子多样性而无法治愈，因此鉴定有助于 GBM 肿瘤发生的分子靶标将适合开发诊断和治疗策略。微小 RNA（miRNA）是一种稳定存在于血液中的小 RNA 分子，在 GBM 的分子过程中发挥着关键作用。因此，本研究旨在调查 GBM 病例中 miR-221 和 miR-222 与健康个体相比的临床作用，并阐明它们在患者生存中的作用。
从 20 例 GBM 病例（治疗前后各 20 例）和 20 例健康个体中抽取血液样本。使用定量 PCR（qPCR）检测所有入组样本中 miR-221 和 miR-222 的表达。使用 Kaplan-Meir 曲线分析所研究的 miR 的敏感性、特异性及其与 GBM 临床特征和患者预后的关系。
与健康个体相比，GBM 病例中 miR-221 和 -222 的表达明显升高（F=12.9，P<0.001，F=28.78，P<0.0001），且具有绝对特异性，miR-221 的敏感性为 90%，miR-222 的敏感性为 85%。在 20 例 GBM 患者中（n=20），miR-221 的平均表达水平随着年龄较大的 GBM（>60 岁）而显著升高，F=5.7，P=0.028，而 miR-221 和 -222 在表现状态（ECGO）方面差异显著，P=0.036 和 0.007，原发性病变患者，P=0.001 和 0.005，手术治疗策略，P<0.001 和 0.004。根据患者的治疗结果将其分为完全缓解（CR）或部分缓解（PR）、稳定疾病（SD）和进展性疾病（PD），miR-221 和 miR-222 的表达随着 PD 而增加，且无进展生存期（PFS）和总生存期（OS）较差的患者是那些高 miR 表达的患者。
循环 miR-221 和 miR-222 的检测可作为诊断 GBM 患者的循环分子标志物，并可预测患者的预后。鼓励进行更大样本量的研究。
