Department of Gerontology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
Department of Endocrinology, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China.
Biomed Res Int. 2020 Aug 4;2020:2837906. doi: 10.1155/2020/2837906. eCollection 2020.
Increasing evidence has shown competitive endogenous RNAs (ceRNAs) play key roles in numerous cancers. Nevertheless, the ceRNA network that can predict the prognosis of lung adenocarcinoma (LUAD) is still lacking. The aim of the present study was to identify the prognostic value of key ceRNAs in lung tumorigenesis. Differentially expressed (DE) RNAs were identified between LUAD and adjacent normal samples by limma package in R using The Cancer Genome Atlas database (TCGA). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway function enrichment analysis was performed using the clusterProfiler package in R. Subsequently, the LUAD ceRNA network was established in three steps based on ceRNA hypothesis. Hub RNAs were identified using degree analysis methods based on Cytoscape plugin cytoHubba. Multivariate Cox regression analysis was implemented to calculate the risk score using the candidate ceRNAs and overall survival information. The survival differences between the high-risk and low-risk ceRNA groups were determined by the Kaplan-Meier and log-rank test using survival and survminer package in R. A total of 2,989 mRNAs, 185 lncRNAs, and 153 miRNAs were identified. GO and KEGG pathway function enrichment analysis showed that DE mRNAs were mainly associated with "sister chromatid segregation," "regulation of angiogenesis," "cell adhesion molecules (CAMs)," "cell cycle," and "ECM-receptor interaction." LUAD-related ceRNA network was constructed, which comprised of 54 nodes and 78 edges. Top ten hub RNAs (hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-340-5p, hsa-miR-377-3p, hsa-miR-21-5p, hsa-miR-326, SNHG1, RALGPS2, and PITX2) were identified according to their degree. Kaplan-Meier survival analyses demonstrated that hsa-miR-21-5p and RALGPS2 had a significant prognostic value. Finally, we found that a high risk of three novel ceRNA interactions (SNHG1-hsa-miR-21-5p-RALGPS2, SNHG1-hsa-miR-326-RALGPS2, and SNHG1-hsa-miR-377-3p-RALGPS2) was positively associated with worse prognosis. Three novel ceRNAs (SNHG1-hsa-miR-21-5p-RALGPS2, SNHG1-hsa-miR-326-RALGPS2, and SNHG1-hsa-miR-377-3p-RALGPS2) might be potential biomarkers for the prognosis and treatment of LUAD.
越来越多的证据表明，竞争性内源性 RNA（ceRNA）在许多癌症中发挥着关键作用。然而，能够预测肺腺癌（LUAD）预后的 ceRNA 网络仍然缺乏。本研究的目的是确定关键 ceRNA 在肺肿瘤发生中的预后价值。使用 R 中的 limma 包，通过癌症基因组图谱数据库（TCGA），在 LUAD 和相邻正常样本之间鉴定差异表达（DE）RNA。使用 R 中的 clusterProfiler 包对基因本体（GO）和京都基因与基因组百科全书（KEGG）途径功能进行富集分析。随后，基于 ceRNA 假说分三步建立 LUAD ceRNA 网络。使用 Cytoscape 插件 cytoHubba 中的度分析方法鉴定核心 RNA。使用候选 ceRNA 和总生存信息，通过多变量 Cox 回归分析计算风险评分。使用 R 中的 survival 和 survminer 包，通过 Kaplan-Meier 和对数秩检验确定高风险和低风险 ceRNA 组之间的生存差异。
总共鉴定出 2989 个 mRNAs、185 个 lncRNAs 和 153 个 miRNAs。GO 和 KEGG 途径功能富集分析表明，DE mRNAs 主要与“姐妹染色单体分离”、“血管生成调节”、“细胞粘附分子（CAMs）”、“细胞周期”和“ECM-受体相互作用”有关。构建了与 LUAD 相关的 ceRNA 网络，该网络包含 54 个节点和 78 个边缘。根据其度，确定了前 10 个核心 RNA（hsa-miR-374a-5p、hsa-miR-374b-5p、hsa-miR-340-5p、hsa-miR-377-3p、hsa-miR-21-5p、hsa-miR-326、SNHG1、RALGPS2 和 PITX2）。Kaplan-Meier 生存分析表明，hsa-miR-21-5p 和 RALGPS2 具有显著的预后价值。最后，我们发现三个新的 ceRNA 相互作用（SNHG1-hsa-miR-21-5p-RALGPS2、SNHG1-hsa-miR-326-RALGPS2 和 SNHG1-hsa-miR-377-3p-RALGPS2）的高风险与预后不良呈正相关。三个新的 ceRNA（SNHG1-hsa-miR-21-5p-RALGPS2、SNHG1-hsa-miR-326-RALGPS2 和 SNHG1-hsa-miR-377-3p-RALGPS2）可能是 LUAD 预后和治疗的潜在生物标志物。
