Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
DNA Cell Biol. 2020 Sep;39(9):1532-1544. doi: 10.1089/dna.2020.5565. Epub 2020 Jul 9.
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.
越来越多的证据表明，异常长链非编码（lnc）RNA 的表达在胃癌（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 名具有 TCGA 胃腺癌（TCGA STAD）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 GSE62254 数据集的 300 名患者组成。为主要队列开发了风险特征和列线图，并在验证队列中进行了验证。此外，还使用基因集富集分析（GSEA）来研究风险特征的通路富集。还在来自 10 名 GC 患者的临床样本中研究了几个 lncRNA 的表达模式。我们确定并验证了一个与 GC 患者 OS 高度相关的 14-lncRNA 特征，该特征在 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 特征是 GC 患者的独立预测因素。因此，构建了一个包含 lncRNA 特征和临床因素的列线图，以预测原发性队列中 GC 患者的 OS，该列线图提示在 TCGA 队列和另外两个验证队列中对生存具有强大的预测值。此外，GSEA 表明，所鉴定的 lncRNAs 可能调节自噬途径，影响 GC 患者的肿瘤发生和预后。实验验证表明，我们的临床样本和 STAD 数据集中 lncRNAs 的表达趋势相同。这些结果表明，风险特征和列线图都是 GC 患者的有效预后指标。
