Department of Gastroenterology, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China.
Department of Pathology, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China.
Mol Genet Genomic Med. 2020 Nov;8(11):e1512. doi: 10.1002/mgg3.1512. Epub 2020 Oct 1.
Stomach adenocarcinoma (STAD), is one of the most lethal malignancies around the world. The aim of this study was to find the long noncoding RNAs (lncRNAs) acting as diagnostic and prognostic biomarker of STAD.
Base on TCGA dataset, the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified between STAD and normal tissue. The machine learning and survival analysis were performed to evaluate the potential diagnostic and prognostic value of lncRNAs for STAD. We also build the co-expression network and functional annotation. The expression of selected candidate mRNAs and lncRNAs were validated by Quantitative real-time polymerase chain reaction (qRT-PCR) and GSE27342 dataset. GSE27342 dataset were also to perform gene set enrichment analysis.
A total of 814 DEmRNAs and 106 DElncRNAs between STAD and normal tissue were obtained. FOXD2-AS1, LINC01235, and RP11-598F7.5 were defined as optimal diagnostic lncRNA biomarkers for STAD. The area under curve (AUC) of the decision tree model, random forests model, and support vector machine (SVM) model were 0.797, 0.981, and 0.983, and the specificity and sensitivity of the three model were 75.0% and 97.1%, 96.9% and 96%, and 96.9% and 97.1%, respectively. Among them, LINC01235 was not only an optimal diagnostic lncRNA biomarkers, but also related to survival time. The expression of three DEmRNAs (ESM1, WNT2, and COL10A1) and three optimal diagnostic lncRNAs biomarkers (FOXD2-AS1, RP11-598F7.5, and LINC01235) in qRT-PCR validation was were consistent with our integrated analysis. Except for FOXD2-AS1, ESM1, WNT2, COL10A1, and LINC01235 were upregulated in STAD, which was consistent with our integration results. Gene set enrichment analysis results indicated that DNA replication, Cell cycle, ECM-receptor interaction, and P53 signaling pathway were four significantly enriched pathways in STAD.
Our study identified three DElncRNAs as potential diagnostic biomarkers of STAD. Among them, LINC01235 also was a prognostic lncRNA biomarkers.
胃腺癌（STAD）是全球最致命的恶性肿瘤之一。本研究旨在寻找作为 STAD 诊断和预后生物标志物的长链非编码 RNA（lncRNA）。
基于 TCGA 数据集，鉴定了 STAD 与正常组织之间差异表达的信使 RNA（DEmRNAs）和 lncRNA（DElncRNAs）。采用机器学习和生存分析评估 lncRNA 对 STAD 潜在的诊断和预后价值。我们还构建了共表达网络和功能注释。通过定量实时聚合酶链反应（qRT-PCR）和 GSE27342 数据集验证了选定候选 mRNAs 和 lncRNAs 的表达。GSE27342 数据集还进行了基因集富集分析。
共获得 814 个 DEmRNAs 和 106 个 DElncRNAs 在 STAD 与正常组织之间。FOXD2-AS1、LINC01235 和 RP11-598F7.5 被定义为 STAD 的最佳诊断 lncRNA 生物标志物。决策树模型、随机森林模型和支持向量机（SVM）模型的曲线下面积（AUC）分别为 0.797、0.981 和 0.983，三个模型的特异性和敏感性分别为 75.0%和 97.1%、96.9%和 96.0%、96.9%和 97.1%。其中，LINC01235 不仅是最佳诊断 lncRNA 生物标志物，而且与生存时间相关。qRT-PCR 验证中三个 DEmRNAs（ESM1、WNT2 和 COL10A1）和三个最佳诊断 lncRNA 生物标志物（FOXD2-AS1、RP11-598F7.5 和 LINC01235）的表达与我们的综合分析一致。除了 FOXD2-AS1，ESM1、WNT2、COL10A1 和 LINC01235 在 STAD 中上调，这与我们的整合结果一致。基因集富集分析结果表明，DNA 复制、细胞周期、ECM-受体相互作用和 P53 信号通路是 STAD 中四个显著富集的通路。
本研究鉴定了三个 DElncRNA 作为 STAD 的潜在诊断生物标志物。其中，LINC01235 也是一种预后 lncRNA 生物标志物。
