Background. Gastric cancer (GC) is a malignant tumour that originates in the gastric mucosal epithelium and is associated with high mortality rates worldwide. Long noncoding RNAs (lncRNAs) have been identified to play an important role in the development of various tumours, including GC. Yet, lncRNA biomarkers in a competing endogenous RNA network (ceRNA network) that are used to predict survival prognosis remain lacking. The aim of this study was to construct a ceRNA network and identify the lncRNA signature as prognostic factors for survival prediction. Methods. The lncRNAs with overall survival significance were used to construct the ceRNA network. Function enrichment, protein-protein interaction, and cluster analysis were performed for dysregulated mRNAs. Multivariate Cox proportional hazards regression was performed to screen the potential prognostic lncRNAs. RT-qPCR was used to measure the relative expression levels of lncRNAs in cell lines. CCK8 assay was used to assess the proliferation of GC cells transfected with sh-lncRNAs. Results. Differentially expressed genes were identified including 585 lncRNAs, 144 miRNAs, and 2794 mRNAs. The ceRNA network was constructed using 35 DElncRNAs associated with overall survival of GC patients. Functional analysis revealed that these dysregulated mRNAs were enriched in cancer-related pathways, including TGF-beta, Rap 1, calcium, and the cGMP-PKG signalling pathway. A multivariate Cox regression analysis and cumulative risk score suggested that two of those lncRNAs (LINC01644 and LINC01697) had significant prognostic value. Furthermore, the results indicate that LINC01644 and LINC01697 were upregulated in GC cells. Knockdown of LINC01644 or LINC01697 suppressed the proliferation of GC cells. Conclusions. The authors identified 2-lncRNA signature in ceRNA regulatory network as prognostic biomarkers for the prediction of GC patient survival and revealed that silencing LINC01644 or LINC01697 inhibited the proliferation of GC cells.

中文翻译：

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lncRNA 相关 ceRNA 网络的综合分析确定了两个 lncRNA 特征作为胃癌的预后生物标志物

背景。胃癌（GC）是一种起源于胃黏膜上皮细胞的恶性肿瘤，在全球范围内与高死亡率相关。已确定长链非编码 RNA (lncRNA) 在包括 GC 在内的各种肿瘤的发展中发挥重要作用。然而，用于预测生存预后的竞争性内源性 RNA 网络（ceRNA 网络）中的 lncRNA 生物标志物仍然缺乏。本研究的目的是构建一个 ceRNA 网络，并将 lncRNA 特征识别为生存预测的预后因素。方法. 具有总体生存意义的 lncRNA 用于构建 ceRNA 网络。对失调的 mRNA 进行功能富集、蛋白质-蛋白质相互作用和聚类分析。进行多变量 Cox 比例风险回归以筛选潜在的预后 lncRNA。RT-qPCR用于测量细胞系中lncRNA的相对表达水平。CCK8 测定用于评估转染 sh-lncRNAs 的 GC 细胞的增殖。结果. 鉴定出差异表达基因，包括 585 个 lncRNA、144 个 miRNA 和 2794 个 mRNA。ceRNA 网络是使用 35 个与 GC 患者总生存期相关的 DElncRNA 构建的。功能分析显示，这些失调的 mRNA 富含癌症相关通路，包括 TGF-β、Rap 1、钙和 cGMP-PKG 信号通路。多变量 Cox 回归分析和累积风险评分表明，其中两个 lncRNA（LINC01644 和 LINC01697）具有显着的预后价值。此外，结果表明 LINC01644 和 LINC01697 在 GC 细胞中上调。LINC01644 或 LINC01697 的敲低抑制了 GC 细胞的增殖。结论. 作者将 ceRNA 调控网络中的 2-lncRNA 特征鉴定为预测 GC 患者存活率的预后生物标志物，并揭示沉默 LINC01644 或 LINC01697 抑制了 GC 细胞的增殖。