Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, China.
Cancer Med. 2017 Jun;6(6):1154-1164. doi: 10.1002/cam4.1047. Epub 2017 Apr 26.
Long noncoding RNAs (lncRNAs) have emerged as essential players in gene regulation. An ever-increasing number of lncRNAs has been found to be associated with the biogenesis and prognosis of gastric cancer (GC). We aimed to develop an lncRNA signature with prognostic value for survival outcomes of GC. Using an lncRNA mining approach, we analyzed the lncRNA expression profiles of 492 GC patients from the Gene Expression Omnibus (GEO), which consisted of the GSE62254 set (N = 300) and the GSE15459 set (N = 192). The associations between the lncRNAs' expression and survival outcome were evaluated. A set of three lncRNAs (LINC01140, TGFB2-OT1, and RP11-347C12.10) was identified to significantly correlate with overall survival. These lncRNAs were then combined to form a single prognostic signature. Based on this three-lncRNA expression signature, patients in the GSE62254 set were classified into high- and low-risk subgroups with significantly different overall survival (hazard ratio [HR] = 1.93, P < 0.001) and disease-free survival (HR = 1.91, P < 0.001). Good reproducibility for the prognostic value of this lncRNA signature was confirmed in the GSE15459 set. Further analysis showed that the prognostic value of this signature was independent of some clinical characteristics. Gene set enrichment analysis indicated that high-risk scores positively related to several molecular pathways of cancer metastasis. Our results suggest that this innovative lncRNA expression signature may be a useful biomarker for the prognosis of patients with GC based on bioinformatics analysis.
长链非编码 RNA（lncRNA）已成为基因调控的重要参与者。越来越多的 lncRNA 被发现与胃癌（GC）的发生和预后有关。我们旨在开发一种具有 lncRNA 签名的预后价值，以预测 GC 患者的生存结果。使用 lncRNA 挖掘方法，我们分析了来自基因表达综合数据库（GEO）的 492 例 GC 患者的 lncRNA 表达谱，该数据库包括 GSE62254 数据集（N=300）和 GSE15459 数据集（N=192）。评估了 lncRNA 表达与生存结果之间的关联。确定了一组三个 lncRNA（LINC01140、TGFB2-OT1 和 RP11-347C12.10）与总生存期显著相关。然后将这些 lncRNA 组合成一个单一的预后签名。基于这三个 lncRNA 表达签名，GSE62254 数据集的患者被分为高风险和低风险亚组，总生存期（风险比 [HR] = 1.93，P < 0.001）和无病生存期（HR = 1.91，P < 0.001）有显著差异。该 lncRNA 签名预后价值在 GSE15459 数据集得到了良好的重现性。进一步分析表明，该签名的预后价值独立于一些临床特征。基因集富集分析表明，高风险评分与癌症转移的几个分子途径呈正相关。我们的研究结果表明，基于生物信息学分析，这种创新的 lncRNA 表达签名可能是预测 GC 患者预后的有用生物标志物。
