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多形性胶质母细胞瘤术后放疗敏感与抵抗患者中微小RNA的差异表达

Differential expression of microRNAs in postoperative radiotherapy sensitive and resistant patients with glioblastoma multiforme.

作者信息

Wu He-Ming, Wang Han-Dong, Tang Yong, Fan You-Wu, Hu Yue-Bing, Tohti Mamatemin, Hao Xiao-Ke, Wei Wu-Ting, Wu Yong

机构信息

Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People's Republic of China.

出版信息

Tumour Biol. 2015 Jun;36(6):4723-30. doi: 10.1007/s13277-015-3121-z. Epub 2015 Mar 11.

Abstract

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and more resistant to radiotherapy. However, hetero-radiosensitivity occurs in different patients. MicroRNAs (miRNAs) play important roles in the initiation and progression of a multitude of tumors. The study aims to examine the different microRNAs expression profiles of postoperative radiotherapy sensitive and resistant patients with GBM, to make an inquiry about their potential role and discover a certain set of radio-sensitivity markers. Three paired samples from six GBM patients who had only been treated with postoperative radiotherapy were selected, and then, they were divided into radiotherapy sensitive group and resistant group according to their overall survivals, local recurrence rates, and Karnofsky Performance Scale scores. Expression profiles of miRNAs in these two groups were determined by the method of microarray assay. Comparing with resistant patients, 13 miRNAs were significantly upregulated and 10 miRNAs were greatly downregulated in sensitive group. Among them, four miRNAs were validated by quantitative RT-PCR. The differentially expressed miRNAs and their putative target genes were revealed by bioformatic analysis to play a role in cell signaling, proliferation, aging, and death. High-enrichment pathway analysis identified that some classical pathways participated in numerous metabolic processes, especially in cell cycle regulation, such as mTOR, MAPK, TGF-beta, and PI3K-Akt signaling pathways. Our research will contribute to identifying clinical diagnostic markers and therapeutic targets in the treatment of GBM by postoperative radiotherapy.

摘要

多形性胶质母细胞瘤(GBM)是最恶性的原发性脑肿瘤,对放疗更具抗性。然而,不同患者存在异质性放射敏感性。微小RNA(miRNA)在多种肿瘤的发生和发展中起重要作用。本研究旨在检测GBM术后放疗敏感和抗性患者不同的微小RNA表达谱,探究其潜在作用并发现一组放射敏感性标志物。选取6例仅接受术后放疗的GBM患者的3对样本,然后根据其总生存期、局部复发率和卡氏功能状态评分将其分为放疗敏感组和抗性组。通过微阵列分析方法确定这两组中miRNA的表达谱。与抗性患者相比,敏感组中有13种miRNA显著上调,10种miRNA显著下调。其中,4种miRNA通过定量RT-PCR进行了验证。生物信息学分析揭示了差异表达的miRNA及其推定的靶基因在细胞信号传导、增殖、衰老和死亡中发挥作用。高富集通路分析确定一些经典通路参与众多代谢过程,尤其是细胞周期调控,如mTOR、MAPK、TGF-β和PI3K-Akt信号通路。我们的研究将有助于识别GBM术后放疗治疗中的临床诊断标志物和治疗靶点。

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