Comprehensive Profiling of lincRNAs in Lung Adenocarcinoma of Never Smokers Reveals Their Roles in Cancer Development and Prognosis.

Comprehensive Profiling of lincRNAs in Lung Adenocarcinoma of Never Smokers Reveals Their Roles in Cancer Development and Prognosis.
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对从不吸烟者肺腺癌中 lincRNA 的全面分析揭示了它们在癌症发展和预后中的作用

DOI:
10.3390/genes8110321
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发表时间:
2017-11-13
期刊:
影响因子:
3.5
通讯作者:
Sun Z
Sun Z
中科院分区:
生物学3区
文献类型:
--
作者:
Li Y;Wang Z;Nair A;Song W;Yang P;Zhang X;Sun Z

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长基因间非编码RNA(lincRNA)是基因转录物家族,其功能在很大程度上未知。虽然吸烟是肺癌的主要原因,但非吸烟者的肺癌是一个独立的实体,其根本原因鲜为人知。越来越多的证据表明lincRNA在癌症的发展和进展中起着重要作用;然而,对于非吸烟者或从不吸烟的人的肺癌,缺乏这样的数据。本研究对来自患有肺腺癌的非吸烟者患者的RNA测序(RNA-seq)数据的lincRNA进行了全面分析。已知的和新的lincRNA都将肿瘤与正常组织明显分离。大约三分之一的lincRNA在肿瘤和正常样品之间差异表达,其中大部分与其推定的蛋白质基因靶点相协调。更重要的是,lincRNA定义了两个与肿瘤侵袭性和患者生存相关的肿瘤簇。我们鉴定了一个lincRNA亚组,其差异表达并且也与患者存活相关。在85个转录组的癌症基因组图谱(TCGA)验证组中观察到差异表达的lincRNA具有非常高的一致性(R2 = 0.9),并且与来自发现组的存活相关的lincRNA在验证组中具有类似的预测性。这些lincRNA作为潜在的诊断和预后标志物值得进一步研究。
Long intergenic non-coding RNA (lincRNA) is a family of gene transcripts, the functions of which are largely unknown. Although cigarette smoking is the main cause for lung cancer, lung cancer in non-smokers is a separate entity and its underlying cause is little known. Growing evidence suggests lincRNAs play a significant role in cancer development and progression; however, such data is lacking for lung cancer in non-smokers, or those who have never smoked. This study conducted comprehensive profiling of lincRNAs from RNA sequencing (RNA-seq) data of non-smoker patients with lung adenocarcinoma. Both known and novel lincRNAs distinctly segregated tumors from normal tissues. Approximately one third of lincRNAs were differentially expressed between tumors and normal samples and most of them were coordinated with their putative protein gene targets. More importantly, lincRNAs defined two clusters of tumors that were associated with tumor aggressiveness and patient survival. We identified a subset of lincRNAs that were differentially expressed and also associated with patient survival. Very high concordance (R2 = 0.9) was observed for the differentially expressed lincRNAs in the Cancer Genome Atlas (TCGA) validation set of 85 transcriptomes and the lincRNAs associated with survival from the discovery set were similarly predictive in the validation set. These lincRNAs warrant further investigation as potential diagnostic and prognostic markers.
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