Increasing evidence suggests that aberrant long noncoding (lnc) RNA expression plays a vital role in gastric cancer (GC) initiation and progression. Thus, we aimed to develop a lncRNA-based risk signature and nomogram to predict overall survival (OS) for patients with GC. Our primary cohort was composed of 341 patients with clinical and lncRNA expression data in The Cancer Genome Atlas stomach adenocarcinoma (TCGA STAD), the internal validation cohort was composed of 172 randomly assigned patients, and the external validation cohort was composed of 300 patients from GSE62254 dataset. A risk signature and nomogram were developed for the primary cohort and validated on the validation cohorts. Furthermore, gene set enrichment analysis (GSEA) was used to investigate the pathway enrichment for the risk signature. The expression patterns of several lncRNAs were also investigated in clinical samples from 10 GC patients. We identified and validated a 14-lncRNA signature highly associated with the OS of patients with GC, which performed well on evaluation with C-index, area under the curve, and calibration curves. In addition, univariate and multivariate Cox regression analyses indicated that the lncRNA signature was an independent predictive factor for GC patients. Therefore, a nomogram incorporating lncRNA signature and clinical factors was constructed to predict OS for patients with GC in primary cohort that suggested powerful predictive values for survival in the TCGA cohort and the other two validation cohorts. In addition, GSEA indicated that the identified lncRNAs may regulate the autophagy pathway, affecting tumorigenesis and prognosis of patients with GC. Experimental validation demonstrated that the expression of lncRNAs showed the same trend both in our clinical samples and STAD dataset. These results suggest that both risk signature and nomogram were effective prognostic indicators for patients with GC.

中文翻译：

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14-lncRNA签名的鉴定和预测胃癌总体生存的预后诺法图的构建。

越来越多的证据表明，异常的长期非编码（lnc）RNA表达在胃癌（GC）的发生和发展中起着至关重要的作用。因此，我们旨在开发基于lncRNA的风险特征图和列线图，以预测GC患者的总生存期（OS）。我们的主要队列由341位癌症基因组图谱胃腺癌（TCGA STAD）中具有临床和lncRNA表达数据的患者组成，内部验证队列由172名随机分配的患者组成，外部验证队列由300名来自GSE62254的患者组成数据集。为主要队列开发了风险签名和列线图，并在验证队列中进行了验证。此外，基因集富集分析（GSEA）用于研究风险签名的途径富集。还从10名GC患者的临床样本中研究了几种lncRNA的表达模式。我们鉴定并验证了与GC患者的OS高度相关的14-lncRNA标记，该标记在C指数，曲线下面积和校准曲线的评估中表现良好。此外，单因素和多因素Cox回归分析表明，lncRNA信号是GC患者的独立预测因素。因此，构建了包含lncRNA特征和临床因素的列线图来预测原发性GC患者的OS，这为TCGA和其他两个验证人群的生存提供了有力的预测价值。此外，GSEA指出，鉴定出的lncRNA可能会调节自噬途径，影响GC患者的肿瘤发生和预后。实验验证表明，在我们的临床样本和STAD数据集中，lncRNA的表达都显示出相同的趋势。这些结果表明，风险签名和列线图均是GC患者的有效预后指标。