一个包含四个 miRNA 的标志物可预测多形性胶质母细胞瘤患者的生存情况。

A 4-miRNAs signature predicts survival in glioblastoma multiforme patients.

机构信息

Institute of Neurology, The Second Hospital, Lanzhou University, Lanzhou, Gansu 730030, China.

Department of Neurosurgery, Fudan University Huashan Hospital, Fudan University, Shanghai 20040, China.

出版信息

Cancer Biomark. 2017 Dec 6;20(4):443-452. doi: 10.3233/CBM-170205.

DOI:10.3233/CBM-170205

PMID:28869437

Abstract

BACKGROUND

Although O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation status is an important marker for glioblastoma multiforme (GBM), there is considerable variability in the clinical outcome of patients with similar methylation profles.

OBJECTIVE

We examined whether a MicroRNA (miRNA) signature can be identified for predicting clinical outcomes and helping in treatment decisions.

METHODS

The differentially expressed miRNAs were evaluated in 6 pairs of short- (⩽ 450 days) and long-term survivors (> 450 days) by using microarray. Real time quantitative PCR (qRT-PCR) was applied to further verify screened miRNAs with a greater number of samples (n= 48). Meanwhile, functional interpretation of miRNA profile was carried out based on miRNA-target databases. In addition, MGMT promoter methylation status was tested by means of pyrosequencing (PSQ) testing.

RESULTS

Six miRNAs were upregulated in the long-term survival group (fold change ⩾ 2.0, P< 0.05). The further verification by qRT-PCR indicated that the increase in let-7g-5p, miR-139-5p, miR-17-5p and miR-9-3p level in long-term survivors was statistically significant. Kaplan-Meier survival analysis showed that high expression of a prognostic 4-miRNA signature was significantly associated with good patient survival (p= 0.0012). The signature regulated signaling pathways including Calcium, MAPK, ErbB, mTOR and cell cycle involved in carcinogenesis from glial progenitor cell to primary GBM.

CONCLUSIONS

The 4-miRNA signature was identified as an independent prognostic biomarker that identified patients who have a favorable outcome.

摘要

背景

尽管 O(6)-甲基鸟嘌呤 DNA 甲基转移酶（MGMT）启动子甲基化状态是胶质母细胞瘤（GBM）的重要标志物，但具有相似甲基化谱的患者的临床结局存在相当大的变异性。

目的

我们研究了是否可以确定 MicroRNA（miRNA）特征来预测临床结果并帮助做出治疗决策。

方法

通过微阵列评估 6 对短（≤450 天）和长（>450 天）生存者之间差异表达的 miRNA。使用 real time quantitative PCR（qRT-PCR）进一步验证具有更多样本（n=48）的筛选 miRNA。同时，基于 miRNA-靶数据库进行 miRNA 谱的功能解释。此外，通过焦磷酸测序（PSQ）测试检测 MGMT 启动子甲基化状态。

结果

在长期生存组中上调了 6 个 miRNA（倍数变化 ⩾2.0，P<0.05）。qRT-PCR 的进一步验证表明，长期幸存者中 let-7g-5p、miR-139-5p、miR-17-5p 和 miR-9-3p 水平的增加具有统计学意义。Kaplan-Meier 生存分析表明，高表达预后 4-miRNA 特征与患者良好生存相关（p=0.0012）。该特征调节信号通路，包括钙、MAPK、ErbB、mTOR 和细胞周期，涉及从神经胶质祖细胞到原发性 GBM 的致癌作用。