Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Medicine (Baltimore). 2023 Mar 10;102(10):e33192. doi: 10.1097/MD.0000000000033192.
Lung cancer is one of the most prevalent cancers and the leading cause of cancer-related deaths worldwide; non-small cell lung cancer (NSCLC) comprises approximately 80% of all lung cancer cases. This study aimed to construct a competing endogenous RNA (ceRNA) network and identify prognostic signatures in elderly patients with NSCLC.
We extracted data from elderly patients with NSCLC from The Cancer Genome Atlas and identified differentially expressed (DE) messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to investigate the functions of DEmRNAs. The interactions between RNAs were predicted using starBase, TargetScan, miRTarBase, and miRanda. Cytoscape version 3.0 was used to construct and visualize the lncRNA-miRNA-mRNA ceRNA network. The association between the expression levels of DERNAs in the constructed ceRNA network and overall survival was determined using the survival package in R software. Furthermore, another Gene Expression Omnibus cohort was studied to externally validate the ceRNA network.
In total, 2865 DEmRNAs, 62 DEmiRNAs, and 131 DElncRNAs were identified. Dysregulated mRNAs are enriched in cancer-related processes and pathways. A ceRNA network was constructed using 38 miRNAs, 61 lncRNAs, and 164 mRNAs. Of these, 3 lncRNAs, 3 miRNAs, and 16 mRNAs were closely related to overall survival. The MIR99AHG-hsa-miR-31-5p-PRKCE axis has been identified as a potential ceRNA network involved in the development of NSCLC in elderly individuals. External validation of the MIR99AHG-hsa-miR-31-5p-PRKCE axis in the GSE19804 cohort showed that PRKCE was downregulated and that MIR99AHG was upregulated in the tumor tissues of elderly patients with NSCLC compared with normal lung tissues.
This study provides novel insights into the lncRNA-miRNA-mRNA ceRNA network and reveals potential biomarkers for the diagnosis and prognosis of elderly patients with NSCLC.
肺癌是最常见的癌症之一，也是全球癌症相关死亡的主要原因；非小细胞肺癌（NSCLC）约占所有肺癌病例的 80%。本研究旨在构建竞争内源性 RNA（ceRNA）网络并确定老年 NSCLC 患者的预后特征。
我们从癌症基因组图谱中提取了老年 NSCLC 患者的数据，并鉴定了差异表达的信使 RNA（mRNA）、microRNA（miRNA）和长非编码 RNA（lncRNA）。使用基因本体论和京都基因与基因组百科全书分析来研究差异表达 mRNA 的功能。使用 starBase、TargetScan、miRTarBase 和 miRanda 预测 RNA 之间的相互作用。使用 Cytoscape 版本 3.0 构建和可视化 lncRNA-miRNA-mRNA ceRNA 网络。使用 R 软件中的 survival 包确定构建的 ceRNA 网络中 DERNAs 的表达水平与总生存期之间的关联。此外，还研究了另一个基因表达综合组学队列来外部验证 ceRNA 网络。
共鉴定出 2865 个差异表达的 mRNAs、62 个差异表达的 miRNAs 和 131 个差异表达的 lncRNAs。失调的 mRNAs 富集在癌症相关过程和途径中。使用 38 个 miRNA、61 个 lncRNA 和 164 个 mRNA 构建了 ceRNA 网络。其中，3 个 lncRNA、3 个 miRNA 和 16 个 mRNA 与总生存期密切相关。MIR99AHG-hsa-miR-31-5p-PRKCE 轴已被确定为一个潜在的 ceRNA 网络，涉及老年人群 NSCLC 的发生。在 GSE19804 队列中对 MIR99AHG-hsa-miR-31-5p-PRKCE 轴进行的外部验证表明，与正常肺组织相比，老年 NSCLC 患者的肿瘤组织中 PRKCE 下调，而 MIR99AHG 上调。
本研究提供了 lncRNA-miRNA-mRNA ceRNA 网络的新见解，并揭示了老年 NSCLC 患者诊断和预后的潜在生物标志物。
