Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37203, USA.
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN 46202, USA.
Sci Rep. 2016 Nov 29;6:37821. doi: 10.1038/srep37821.
Breast cancer is a complex disease, characterized by gene deregulation. There is less systematic investigation of the capacity of long intergenic non-coding RNAs (lincRNAs) as biomarkers associated with breast cancer pathogenesis or several clinicopathological variables including receptor status and patient survival. We designed a two-stage study, including 1,000 breast tumor RNA-seq data from The Cancer Genome Atlas (TCGA) as the discovery stage, and RNA-seq data of matched tumor and adjacent normal tissue from 50 breast cancer patients as well as 23 normal breast tissue from healthy women as the replication stage. We identified 83 lincRNAs showing the significant expression changes in breast tumors with a false discovery rate (FDR) < 1% in the discovery dataset. Thirty-seven out of the 83 were validated in the replication dataset. Integrative genomic analyses suggested that the aberrant expression of these 37 lincRNAs was probably related with the expression alteration of several transcription factors (TFs). We observed a differential co-expression pattern between lincRNAs and their neighboring genes. We found that the expression levels of one lincRNA (RP5-1198O20 with Ensembl ID ENSG00000230615) were associated with breast cancer survival with P < 0.05. Our study identifies a set of aberrantly expressed lincRNAs in breast cancer.
乳腺癌是一种复杂的疾病，其特征是基因失调。对于长基因间非编码 RNA（lincRNA）作为与乳腺癌发病机制或包括受体状态和患者生存在内的几个临床病理变量相关的生物标志物的能力，系统研究较少。我们设计了一个两阶段的研究，包括来自癌症基因组图谱（TCGA）的 1000 例乳腺癌肿瘤 RNA-seq 数据作为发现阶段，以及 50 例乳腺癌患者的肿瘤和相邻正常组织的 RNA-seq 数据以及 23 例健康女性的正常乳腺组织作为复制阶段。我们在发现数据集的错误发现率（FDR）<1%的情况下，鉴定出 83 个在乳腺癌肿瘤中表达显著变化的 lincRNA。这 83 个中有 37 个在复制数据集得到验证。综合基因组分析表明，这些 37 个 lincRNA 的异常表达可能与几个转录因子（TF）的表达改变有关。我们观察到 lincRNA 与其相邻基因之间存在差异共表达模式。我们发现，一个 lincRNA（具有 Ensembl ID ENSG00000230615 的 RP5-1198O20）的表达水平与乳腺癌的生存有关，P<0.05。我们的研究确定了一组在乳腺癌中异常表达的 lincRNA。
