Department of Physiology and Biochemistry, School of Medicine, The University of Jordan, Amman, Jordan.
School of Medicine, The University of Jordan, Amman, Jordan.
J Mol Neurosci. 2018 Nov;66(3):307-313. doi: 10.1007/s12031-018-1178-z. Epub 2018 Sep 25.
The current management of ependymoma is wrought with limitations. Molecular classification is a promising development. MicroRNA (miRNA) deregulation is associated with human cancer and may be a means of molecular classification. The aim of our study is to investigate the association of miRNA expression with the clinicopathologic characteristics of ependymoma. Twenty-two samples were clinically annotated. Histologic features were reassessed and the expression of Ki-67, cyclin D1, and nestin was examined. The expression of 84 stem cell-related miRNAs was profiled. The ΔΔC method and a Student's t test were used to compute fold changes and P values, respectively. Our analysis revealed 24 statistically significant associations. We identified seven site-specific miRNAs. The pattern of expression was variable in each anatomic site. In addition, we identified six candidate recurrence biomarkers, all of which were overexpressed in recurrent cases. All three grade-related miRNAs were underexpressed in anaplastic samples. Two miRNAs each were underexpressed in samples immunoreactive to Ki-67 and cyclin D1. No miRNAs were differentially expressed between nestin-negative and nestin-positive samples. In conclusion, molecular alterations in ependymoma involve miRNAs. In our report, we review the level of evidence for the biomarker candidacy of identified miRNAs. Confirmatory studies are necessary to establish robust biomarkers for the clinical management of ependymoma. Proteins regulated by differentially expressed miRNAs are additional candidate biomarkers and may offer targets for novel therapeutic interventions.
目前对室管膜瘤的治疗存在诸多限制。分子分类是一种很有前途的发展方向。microRNA(miRNA)失调与人类癌症有关,可能是一种分子分类的手段。我们的研究旨在探讨 miRNA 表达与室管膜瘤临床病理特征的关系。对 22 个样本进行了临床注释。重新评估了组织学特征,并检查了 Ki-67、cyclin D1 和巢蛋白的表达。对 84 个干细胞相关 miRNA 的表达进行了分析。采用 ΔΔC 法和学生 t 检验分别计算倍数变化和 P 值。我们的分析发现了 24 个具有统计学意义的关联。我们确定了 7 个特定部位的 miRNA。每种解剖部位的表达模式均不同。此外,我们确定了 6 个候选复发生物标志物,所有这些标志物在复发病例中均过表达。所有三种与分级相关的 miRNA 在间变性样本中表达下调。有两个 miRNA 在 Ki-67 和 cyclin D1 免疫反应阳性的样本中表达下调。nestin 阴性和 nestin 阳性样本之间没有差异表达的 miRNA。总之,室管膜瘤中的分子改变涉及 miRNA。在我们的报告中,我们回顾了鉴定 miRNA 的生物标志物候选资格的证据水平。需要进行确证性研究,以建立用于室管膜瘤临床管理的稳健生物标志物。受差异表达 miRNA 调控的蛋白质是另外的候选生物标志物,并且可能为新的治疗干预提供靶标。