Henriksen Michael, Johnsen Kasper Bendix, Olesen Pia, Pilgaard Linda, Duroux Meg
Laboratory for Cancer Biology, Institute of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3B, 9220, Aalborg Ø, Denmark.
Neuromolecular Med. 2014 Sep;16(3):565-77. doi: 10.1007/s12017-014-8309-7. Epub 2014 May 10.
The increasing interest in identifying molecular biomarkers to determine patient prognosis in glioblastoma multiforme (GBM) has resulted in several microRNA (miRNA)-based signatures able to predict progression-free and overall survival. However, the coherency between these signatures is small, and correlations to clinicopathological features other than survival are seldom seen. The aim of this study was to identify any significant relationship between miRNA signatures and clinicopathological data by combining pathological features with miRNA and mRNA analysis in fourteen GBM patients. In total, 161 miRNAs were shown to cluster the GBM tumor samples into long- and short-term-surviving patients. Many of these miRNAs were associated with differential expression in GBM, including a number of miRNAs shown to confer risk or protection with respect to clinical outcome and to modulate the mesenchymal mode of migration and invasion. An inverse relationship between miR-125b and nestin expression was identified and correlated with overall survival in GBM patients, eloquently illustrating how clinicopathological findings and molecular profiling may be a relevant combination to predict patient outcome. The intriguing finding that many of the differentially expressed miRNAs contained exosome-packaging motifs in their mature sequences suggests that we must expand our view to encompass the complex intercellular communication in order to identify molecular prognostic biomarkers and to increase our knowledge in the field of GBM pathogenesis.
人们对识别分子生物标志物以确定多形性胶质母细胞瘤(GBM)患者预后的兴趣日益浓厚,这已产生了几种基于微小RNA(miRNA)的特征,能够预测无进展生存期和总生存期。然而,这些特征之间的一致性很小,与生存以外的临床病理特征的相关性也很少见。本研究的目的是通过将病理特征与14例GBM患者的miRNA和mRNA分析相结合,确定miRNA特征与临床病理数据之间是否存在显著关系。总共161种miRNA被证明可将GBM肿瘤样本聚类为长期和短期存活患者。其中许多miRNA与GBM中的差异表达相关,包括一些显示出与临床结果相关的风险或保护作用以及调节间充质迁移和侵袭模式的miRNA。在GBM患者中,miR-125b与巢蛋白表达之间存在负相关,并与总生存期相关,有力地说明了临床病理发现和分子谱分析如何可能是预测患者预后的相关组合。一个有趣的发现是,许多差异表达的miRNA在其成熟序列中包含外泌体包装基序,这表明我们必须拓宽视野,以涵盖复杂的细胞间通讯,以便识别分子预后生物标志物,并增加我们在GBM发病机制领域的知识。