文章：

早期慢性淋巴细胞白血病中的lncRNA分析揭示了与临床结局相关的转录指纹

lncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome

原文发布日期：2016-09-09

DOI: 10.1038/bcj.2016.77

类型: Original Article

开放获取: 是

英文摘要：

Long non-coding RNAs (lncRNAs) represent a novel class of functional RNA molecules with an important emerging role in cancer. To elucidate their potential pathogenetic role in chronic lymphocytic leukemia (CLL), a biologically and clinically heterogeneous neoplasia, we investigated lncRNAs expression in a prospective series of 217 early-stage Binet A CLL patients and 26 different subpopulations of normal B-cells, through a custom annotation pipeline of microarray data. Our study identified a 24-lncRNA-signature specifically deregulated in CLL compared with the normal B-cell counterpart. Importantly, this classifier was validated on an independent data set of CLL samples. Belonging to the lncRNA signature characterizing distinct molecular CLL subgroups, we identified lncRNAs recurrently associated with adverse prognostic markers, such as unmutated IGHV status, CD38 expression, 11q and 17p deletions, and NOTCH1 mutations. In addition, correlation analyses predicted a putative lncRNAs interplay with genes and miRNAs expression. Finally, we generated a 2-lncRNA independent risk model, based on lnc-IRF2-3 and lnc-KIAA1755-4 expression, able to distinguish three different prognostic groups in our series of early-stage patients. Overall, our study provides an important resource for future studies on the functions of lncRNAs in CLL, and contributes to the discovery of novel molecular markers with clinical relevance associated with the disease.

摘要翻译： 

长链非编码RNA（lncRNAs）作为一类新型功能性RNA分子，在癌症中的作用日益凸显。为阐明其在慢性淋巴细胞白血病（CLL）这种具有高度生物学和临床异质性的肿瘤中的潜在致病机制，我们通过定制微阵列数据注释流程，对217例早期Binet A分期CLL患者及26种不同亚群正常B细胞进行了lncRNAs表达研究。本研究鉴定出24个在CLL中相较于正常B细胞特异性失调的lncRNAs特征谱。值得注意的是，该分类器在独立CLL样本数据集得到了验证。在表征不同CLL分子亚群的lncRNAs特征谱中，我们发现了与不良预后标志物（如未突变IGHV状态、CD38表达、11q和17p缺失、NOTCH1突变）反复相关的lncRNAs。此外，相关性分析预测了lncRNAs与基因及miRNA表达之间可能存在的相互作用。最终，我们基于lnc-IRF2-3和lnc-KIAA1755-4表达构建了包含2个lncRNAs的独立风险模型，该模型能在早期患者队列中区分三种不同预后群体。总体而言，本研究为未来探索lncRNAs在CLL中的功能提供了重要资源，并推动了具有临床意义的疾病相关新型分子标志物的发现。

原文链接：

lncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome