Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Nat Struct Mol Biol. 2013 Jul;20(7):908-13. doi: 10.1038/nsmb.2591. Epub 2013 Jun 2.
Despite growing appreciation of the importance of long noncoding RNAs (lncRNAs) in normal physiology and disease, our knowledge of cancer-related lncRNAs remains limited. By repurposing microarray probes, we constructed expression profiles of 10,207 lncRNA genes in approximately 1,300 tumors over four different cancer types. Through integrative analysis of the lncRNA expression profiles with clinical outcome and somatic copy-number alterations, we identified lncRNAs that are associated with cancer subtypes and clinical prognosis and predicted those that are potential drivers of cancer progression. We validated our predictions by experimentally confirming prostate cancer cell growth dependence on two newly identified lncRNAs. Our analysis provides a resource of clinically relevant lncRNAs for the development of lncRNA biomarkers and the identification of lncRNA therapeutic targets. It also demonstrates the power of integrating publically available genomic data sets and clinical information for discovering disease-associated lncRNAs.
尽管人们越来越认识到长非编码 RNA（lncRNA）在正常生理和疾病中的重要性，但我们对与癌症相关的 lncRNA 的了解仍然有限。通过重新利用微阵列探针，我们构建了大约 1300 个肿瘤中 10207 个 lncRNA 基因的表达谱，涵盖了四种不同的癌症类型。通过将 lncRNA 表达谱与临床结局和体细胞拷贝数改变进行综合分析，我们确定了与癌症亚型和临床预后相关的 lncRNA，并预测了可能是癌症进展的驱动因素的 lncRNA。我们通过实验证实了两个新鉴定的 lncRNA 对前列腺癌细胞生长的依赖性，从而验证了我们的预测。我们的分析为开发 lncRNA 生物标志物和鉴定 lncRNA 治疗靶点提供了具有临床相关性的 lncRNA 资源。它还展示了整合公开可用的基因组数据集和临床信息以发现与疾病相关的 lncRNA 的强大功能。
