Dept. of Cancer Biology and Genetics (CBG), The Ohio State University, Columbus, OH, United States.
CCC - Genomics Shared Resource, The Ohio State University, Columbus, OH, United States.
EBioMedicine. 2018 Apr;30:105-112. doi: 10.1016/j.ebiom.2018.03.022. Epub 2018 Mar 21.
The World Health Organization has recently introduced molecular prognostic-diagnostic biomarkers in the classification of Central Nervous System (CNS) tumors. In order to characterize subclasses of tumors that cannot find a precise location in the current classification, and, or cannot be tested because of scant material, it is important to find new molecular biomarkers in tissue and, or biological fluid samples. In this study, we identified serum microRNAs that could serve as biomarkers for the diagnosis and prognosis of patients with tumors of glial origin. We retrospectively analyzed microRNA expression in the serum extracellular vesicles of patients with tumors of glial origin. Extracellular vesicles RNA was analyzed by Nanostring. qRT-PCR confirmed 6 overexpressed microRNAs: hsa-miR-4443, hsa-miR-422a, hsa-miR-494-3p, hsa-miR-502-5p, hsa-miR-520f-3p, and hsa-miR-549a. Hsa-miR-4443 was the only microRNA that showed significant differences in most comparisons. In situ hybridization (ISH), confirmed that our signature was mostly expressed in cancer cells. Importantly, hsa-miR-549a and hsa-miR-502-5p expression predicted prognosis in patients with tumors of glial origin. Although more studies are needed, we demonstrated that serum vesicles microRNA profiles are promising diagnostic and prognostic molecular biomarkers that will find an actual application in the clinical practice of CNS tumors.
世界卫生组织最近在中枢神经系统(CNS)肿瘤的分类中引入了分子预后诊断生物标志物。为了描述当前分类中无法准确定位的肿瘤亚类,或者由于材料稀少而无法进行测试的肿瘤亚类,找到组织和/或生物液样本中的新分子生物标志物非常重要。在这项研究中,我们确定了可以作为胶质来源肿瘤患者诊断和预后标志物的血清 microRNA。我们回顾性分析了胶质来源肿瘤患者血清细胞外囊泡中的 microRNA 表达。通过 Nanostring 分析细胞外囊泡 RNA。qRT-PCR 证实了 6 个过表达的 microRNA:hsa-miR-4443、hsa-miR-422a、hsa-miR-494-3p、hsa-miR-502-5p、hsa-miR-520f-3p 和 hsa-miR-549a。hsa-miR-4443 是大多数比较中唯一表现出显著差异的 microRNA。原位杂交(ISH)证实我们的特征主要在癌细胞中表达。重要的是,hsa-miR-549a 和 hsa-miR-502-5p 的表达可以预测胶质来源肿瘤患者的预后。尽管还需要更多的研究,但我们证明了血清囊泡 microRNA 谱是很有前途的诊断和预后分子生物标志物,将在 CNS 肿瘤的临床实践中找到实际应用。