Differential expression analysis at the individual level reveals a lncRNA prognostic signature for lung adenocarcinoma.
Differential expression analysis at the individual level reveals a lncRNA prognostic signature for lung adenocarcinoma.
复制标题
个体水平的差异表达分析揭示了肺腺癌的 lncRNA 预后特征
DOI：
10.1186/s12943-017-0666-z
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发表时间：
2017-06-06
期刊：
影响因子：
37.3
通讯作者：
Gu Y
中科院分区：
文献类型：
--
作者：
Peng F;Wang R;Zhang Y;Zhao Z;Zhou W;Chang Z;Liang H;Zhao W;Qi L;Guo Z;Gu Y
研究背景长链非编码RNA（lncRNA）的失调与肿瘤的发生和发展有关。目前的方法只能在群体水平上捕获lncRNA的差异表达，而忽略了个体患者中lncRNA的异质性表达。（LncRIndiv）以鉴定差异表达（DE）通过利用每个疾病样品中lncRNA表达水平的破坏顺序与稳定的正常顺序进行比较，在个体癌症患者中检测lncRNA。肺腺癌（LUAD）。基于LUAD个体水平的DE lncRNAs的表达谱，我们使用了正向选择程序来识别I-II期LUAD患者的预后特征，而无需辅助治疗。基于个体水平的DE lncRNA，我们开发了一种由两种lncRNA组成的稳健的预后标记，（C1 orf 132和TMPO-AS 1）用于未经辅助治疗的I-II期LUAD患者（P= 3.06 × 10−6，对数秩检验），这在GSE 50081的两个独立数据集中得到了证实（P= 1.82 × 10 - 2，对数秩检验）和GSE 31210（P= 7.43 × 10 - 4，对数秩检验）调整其他临床因素后，如吸烟状态和分期。结论LncRIndiv可成功检测LUAD患者的DE lncRNAs，可用于LUAD患者的预后判断。
BackgroundDeregulations of long non-coding RNAs (lncRNAs) have been implicated in cancer initiation and progression. Current methods can only capture differential expression of lncRNAs at the population level and ignore the heterogeneous expression of lncRNAs in individual patients.MethodsWe propose a method (LncRIndiv) to identify differentially expressed (DE) lncRNAs in individual cancer patients by exploiting the disrupted ordering of expression levels of lncRNAs in each disease sample in comparison with stable normal ordering.LncRIndivwas applied to lncRNA expression profiles of lung adenocarcinoma (LUAD). Based on the expression profile of LUAD individual-level DE lncRNAs, we used a forward selection procedure to identify prognostic signature for stage I-II LUAD patients without adjuvant therapy.ResultsIn both simulated data and real pair-wise cancer and normal sample data,LncRIndivmethod showed good performance. Based on the individual-level DE lncRNAs, we developed a robust prognostic signature consisting of two lncRNA (C1orf132andTMPO-AS1) for stage I-II LUAD patients without adjuvant therapy (P= 3.06 × 10−6, log-rank test), which was confirmed in two independent datasets of GSE50081 (P= 1.82 × 10−2, log-rank test) and GSE31210 (P= 7.43 × 10−4, log-rank test) after adjusting other clinical factors such as smoking status and stages. Pathway analysis showed thatTMPO-AS1andC1orf132could affect the prognosis of LUAD patients through regulating cell cycle and cell adhesion.ConclusionsLncRIndivcan successfully detect DE lncRNAs in individuals and be applied to identify prognostic signature for LUAD patients.