Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province, People's Republic of China.
Cancer Med. 2020 Jan;9(1):335-349. doi: 10.1002/cam4.2621. Epub 2019 Nov 19.
Gastric cancer (GC) remains an important malignancy worldwide with poor prognosis. Long noncoding RNAs (lncRNAs) can markedly affect cancer progression. Moreover, lncRNAs have been proposed as diagnostic or prognostic biomarkers of GC. Therefore, the current study aimed to explore lncRNA-based prognostic biomarkers for GC. LncRNA expression profiles from the Gene Expression Omnibus (GEO) database were first downloaded. After re-annotation of lncRNAs, a univariate Cox analysis identified 177 prognostic lncRNA probes in the training set GSE62254 (n = 225). Multivariate Cox analysis of each lncRNA with clinical characteristics as covariates identified a total of 46 prognostic lncRNA probes. Robust likelihood-based survival and least absolute shrinkage and selection operator (LASSO) models were used to establish a 6-lncRNA signature with prognostic value. Receiver operating characteristic (ROC) curve analyses were employed to compare survival prediction in terms of specificity and sensitivity. Patients with high-risk scores exhibited a significantly worse overall survival (OS) than patients with low-risk scores (log-rank test P-value <.0001), and the area under the ROC curve (AUC) for 5-year survival was 0.77. A nomogram and forest plot were constructed to compare the clinical characteristics and risk scores by a multivariable Cox regression analysis, which suggested that the 6-lncRNA signature can independently make the prognosis evaluation of patients. Single-sample GSEA (ssGSEA) was used to determine the relationships between the 6-lncRNA signature and biological functions. The internal validation set GSE62254 (n = 75) and the external validation set GSE57303 (n = 70) were successfully used to validate the robustness of our 6-lncRNA signature. In conclusion, based on the above results, the 6-lncRNA signature can effectively make the prognosis evaluation of GC patients.
胃癌（GC）仍然是全球一种预后不良的重要恶性肿瘤。长链非编码 RNA（lncRNA）可以显著影响癌症的进展。此外，lncRNA 已被提议作为 GC 的诊断或预后生物标志物。因此，本研究旨在探索基于 lncRNA 的 GC 预后生物标志物。首先从基因表达综合数据库（GEO）下载 lncRNA 表达谱。lncRNA 重新注释后，单因素 Cox 分析在训练集 GSE62254（n=225）中确定了 177 个预后 lncRNA 探针。将每个 lncRNA 与临床特征作为协变量进行多因素 Cox 分析，共确定了 46 个预后 lncRNA 探针。使用稳健似然生存和最小绝对收缩和选择算子（LASSO）模型建立具有预后价值的 6-lncRNA 特征。接收器操作特征（ROC）曲线分析用于比较特异性和敏感性的生存预测。高风险评分的患者总生存期（OS）明显差于低风险评分的患者（对数秩检验 P 值<.0001），5 年生存率的 ROC 曲线下面积（AUC）为 0.77。构建列线图和森林图，通过多变量 Cox 回归分析比较临床特征和风险评分，提示 6-lncRNA 特征可独立对患者预后进行评估。单样本 GSEA（ssGSEA）用于确定 6-lncRNA 特征与生物学功能之间的关系。内部验证集 GSE62254（n=75）和外部验证集 GSE57303（n=70）成功用于验证我们的 6-lncRNA 特征的稳健性。总之，基于上述结果，6-lncRNA 特征可有效对 GC 患者进行预后评估。
