Department of Respiratory Medicine, Jingmen No. 2 People's Hospital, Jingmen, Hubei, China.
Department of Utrasound, Jingmen No. 2 People's Hospital, Jingmen, Hubei, China.
J Cell Biochem. 2019 Sep;120(9):15730-15739. doi: 10.1002/jcb.28842. Epub 2019 May 3.
Long noncoding RNA (lncRNA) has been increasingly reported to play crucial roles in cancer development. In this study, we aim to develop a lncRNA-based signature to predict the relapse of early-stage (stage I-II) lung adenocarcinoma (LUAD).
With a lncRNA-mining strategy, lncRNA expression profiles of three LUAD cohorts were obtained from the Gene Expression Omnibus database. A risk score model was established based on the lncRNAs expression from training set (GSE31210, n = 204) and further validated in two independent testing sets (GSE50081, n = 124; and GSE30219, n = 84). The potential signaling pathways modulated by the prognostic lncRNAs were explored using bioinformatics analysis.
In the training set, seven lncRNAs were identified to be significantly correlated with the relapse-free survival (RFS) of early-stage LUAD, and were then aggregated to form a seven-lncRNA prognostic signature to classify patients into high-risk and low-risk groups. Individuals of training set in the high-risk group exhibited a poorer RFS than those in the low-risk group (HR: 7.574, 95% CI: 4.165-13.775; P < 0.001). The similar prognostic powers of the seven-lncRNA signature were also achieved in the two independent testing sets and in stratified analysis. Multivariate Cox regression indicated that the prognostic value of seven-lncRNA signature was independent of other clinical features. Functional enrichment analysis found that the seven-lncRNA signature may be involved in biological pathways such as cell cycle, DNA replication, and p53 signaling pathway.
Our results indicate that the seven-lncRNA signature may be an innovative biomarker to predict the relapse of early-stage LUAD.
长链非编码 RNA（lncRNA）在癌症发展中发挥着关键作用，这一观点已得到越来越多的报道。本研究旨在建立基于 lncRNA 的签名预测早期肺腺癌（LUAD）复发的模型。
通过 lncRNA 挖掘策略，从 GEO 数据库中获得了三个 LUAD 队列的 lncRNA 表达谱。基于训练集（GSE31210，n=204）lncRNA 表达数据，建立风险评分模型，然后在两个独立的测试集（GSE50081，n=124；GSE30219，n=84）中进行验证。使用生物信息学分析探索预测预后 lncRNAs 调控的潜在信号通路。
在训练集中，鉴定出 7 个与早期 LUAD 无复发生存（RFS）显著相关的 lncRNA，这些 lncRNA 被聚合到一个由 7 个 lncRNA 组成的预后签名中，用于将患者分为高危组和低危组。高危组患者的 RFS 明显低于低危组（HR：7.574，95%CI：4.165-13.775；P<0.001）。该 7-lncRNA 签名在两个独立测试集和分层分析中也具有相似的预后能力。多变量 Cox 回归分析表明，7-lncRNA 签名的预后价值独立于其他临床特征。功能富集分析发现，7-lncRNA 签名可能参与细胞周期、DNA 复制和 p53 信号通路等生物学途径。
我们的研究结果表明，7-lncRNA 签名可能是预测早期 LUAD 复发的一种创新性生物标志物。
