Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing, Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China.
Clin Transl Gastroenterol. 2019 Jan;10(1):e00004. doi: 10.14309/ctg.0000000000000004.
Molecular prognostic biomarkers for gastric cancer (GC) are still limited. We aimed to identify potential messenger RNAs (mRNAs) associated with GC prognosis and further establish an mRNA signature to predict the survival of GC based on the publicly accessible databases.
Discovery of potential mRNAs associated with GC survival was undertaken for 441 patients with GC based on the Cancer Genome Atlas (TCGA), with information on clinical characteristics and vital status. Gene ontology functional enrichment analysis and pathway enrichment analysis were conducted to interrogate the possible biological functions. We narrowed down the list of mRNAs for validation study based on a significance level of 1.00 × 10, also integrating the information from the methylation analysis and constructing the protein-protein interaction network for elucidating biological processes. A total of 54 mRNAs were further studied in the validation stage, using the Gene Expression Omnibus (GEO) database (GSE84437, n = 433). The validated mRNAs were used to construct a risk score model predicting the prognosis of GC.
A total of 13 mRNAs were significantly associated with survival of GC, after the validation stage, including DCLK1, FLRT2, MCC, PRICKLE1, RIMS1, SLC25A15, SLCO2A1, CDO1, GHR, CD109, SELP, UPK1B, and CD36. Except CD36, DCLK1, and SLCO2A1, other mRNAs are newly reported to be associated with GC survival. The 13 mRNA-based risk score had good performance on distinguishing GC prognosis, with a higher score indicating worse survival in both TCGA and GEO datasets.
We established a 13-mRNA signature to potentially predict the prognosis of patients with GC, which might be useful in clinical practice for informing patient stratification.
胃癌（GC）的分子预后生物标志物仍然有限。我们旨在确定与 GC 预后相关的潜在信使 RNA（mRNA），并进一步基于公开可访问的数据库建立预测 GC 患者生存的 mRNA 特征。
根据癌症基因组图谱（TCGA）中 441 名 GC 患者的临床特征和生存状态信息，进行与 GC 生存相关的潜在 mRNAs 的发现。进行基因本体功能富集分析和通路富集分析，以探究可能的生物学功能。我们根据 1.00×10 的显著性水平，缩小了验证研究的 mRNAs 列表，同时整合了甲基化分析信息并构建蛋白质-蛋白质相互作用网络，以阐明生物学过程。在验证阶段，我们使用基因表达综合数据库（GEO）（GSE84437，n=433）进一步研究了总共 54 个 mRNAs。验证的 mRNAs 用于构建预测 GC 预后的风险评分模型。
经过验证阶段，共有 13 个 mRNAs 与 GC 患者的生存显著相关，包括 DCLK1、FLRT2、MCC、PRICKLE1、RIMS1、SLC25A15、SLCO2A1、CDO1、GHR、CD109、SELP、UPK1B 和 CD36。除 CD36、DCLK1 和 SLCO2A1 外，其他 mRNAs 是新报道与 GC 生存相关的。基于 13 个 mRNA 的风险评分在区分 GC 预后方面具有良好的性能，评分越高，TCGA 和 GEO 数据集的生存情况越差。
我们建立了一个 13-mRNA 特征，可以潜在预测 GC 患者的预后，这可能有助于临床实践中的患者分层。
