College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.
Division of Biostatistics, Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL.
Int J Cancer. 2018 Nov 1;143(9):2150-2160. doi: 10.1002/ijc.31573. Epub 2018 Jul 28.
Long non-coding RNAs (lncRNAs) are a major class of non-coding RNAs, and the functional deregulations of lncRNAs have been shown to be associated with the development and progression of BC. In this work, we conduct an integrative analysis on five re-annotated lncRNA expression datasets from the Gene Expression Omnibus (GEO) which included a total of 891 BC samples. We identified a five-lncRNA signature that was significantly associated with DFS in the training cohort of 327 patients. We found the five-lncRNA signature could effectively stratify patients in the training dataset into high- and low-risk groups with significantly different DFS (p = 3.29 × 10 , log-rank test). The five-lncRNA signature was effectively validated in four independent cohorts, and prognostic analysis results showed that the five-lncRNA signature was independent of clinical prognostic factors, such as BC subtypes and adjuvant treatments. Furthermore, GSEA suggested that the five-lncRNA signature was involved in BC metastasis-related pathways. Our findings indicate that these five lncRNAs may be implicated in BC pathogenesis, and further, these lncRNAs may potentially serve as novel candidate biomarkers for the identification of BC patients at high risk for tumor recurrence.
长链非编码 RNA(lncRNAs)是一类主要的非编码 RNA,lncRNAs 的功能失调已被证明与 BC 的发生和发展有关。在这项工作中,我们对 GEO 中五个重新注释的 lncRNA 表达数据集进行了综合分析,这些数据集共包含 891 个 BC 样本。我们确定了一个五 lncRNA 特征,该特征与 327 例患者训练队列中的 DFS 显著相关。我们发现,该五 lncRNA 特征可以有效地将训练数据集中的患者分为高风险和低风险组,两组的 DFS 差异具有统计学意义(p=3.29×10-5,对数秩检验)。该五 lncRNA 特征在四个独立的队列中得到了有效验证,预后分析结果表明,该五 lncRNA 特征独立于临床预后因素,如 BC 亚型和辅助治疗。此外,GSEA 表明该五 lncRNA 特征与 BC 转移相关途径有关。我们的研究结果表明,这五个 lncRNAs 可能与 BC 的发病机制有关,并且这些 lncRNAs 可能潜在地作为识别肿瘤复发风险高的 BC 患者的新型候选生物标志物。