Su Haiyang, Lin Zhenyang, Peng Weicheng, Hu Zhiqiang
Department of Neurosurgery, Peking University Ninth School of Clinical Medicine, Beijing 100038, P.R. China.
Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
Oncol Lett. 2019 Feb;17(2):2228-2236. doi: 10.3892/ol.2018.9829. Epub 2018 Dec 14.
Brain metastases originating from lung adenocarcinoma (LAD) occur frequently. The aim of the current study was to assess potential biomarkers for the prognosis of lung adenocarcinoma brain metastasis (LAD-BM) through the analysis of gene expression microarrays. The current study downloaded two gene expression datasets, GSE14108 and GSE10245, from the Gene Expression Omnibus database. From GSE14108 and GSE10245, 19 LAD-BM samples and 40 primary LAD samples were selected for analysis. To identify the differentially expressed genes (DEGs), the current study compared the two sample groups, using the limma R package. Subsequently, pathway enrichment analysis was conducted using the Cluster Profiler R package, and the construction of the protein-protein interaction (PPI) network was executed utilizing the Search Tool for the Retrieval of Interacting Genes database. The microRNA-target network was built using the TargetScore R package. Then, these networks were established and visualized using Cytoscape software. An array of 463 DEGs was identified in the LAD-BM samples, including 256 upregulated and 207 downregulated genes. Based on functional term enrichment analysis using the Gene Ontology database and signaling pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes database, it was identified that the overlapping DEGs were primarily involved in chemokine-associated signal transduction, which may mediate lung cancer cell metastasis to the brain. Chemokine ligand 2, lysozyme, matrix metalloproteinase-2 (MMP-2), lysyl oxidase (LOX) and granzyme B were identified as potential biomarkers according to a topological analysis of the PPI networks. Two notable nodes, MMP-2 and LOX, appeared in the PPI network and were key points in the microRNA-target network, as they were regulated by hsa-let-7d. Many DEGs and microRNAs were regarded as prognostic biomarkers for lung adenocarcinoma metastasis in the current study. These DEGs were primarily associated with chemokine-mediated signaling pathways. In addition, MMP-2 and LOX were predicted to be targets of hsa-let-7d.
源自肺腺癌（LAD）的脑转移瘤很常见。本研究的目的是通过基因表达微阵列分析评估肺腺癌脑转移（LAD - BM）预后的潜在生物标志物。本研究从基因表达综合数据库下载了两个基因表达数据集，GSE14108和GSE10245。从GSE14108和GSE10245中，选取了19个LAD - BM样本和40个原发性LAD样本进行分析。为了鉴定差异表达基因（DEG），本研究使用limma R包比较了两个样本组。随后，使用Cluster Profiler R包进行通路富集分析，并利用检索相互作用基因数据库的搜索工具构建蛋白质 - 蛋白质相互作用（PPI）网络。使用TargetScore R包构建微小RNA - 靶标网络。然后，使用Cytoscape软件建立并可视化这些网络。在LAD - BM样本中鉴定出一系列463个DEG，包括256个上调基因和207个下调基因。基于使用基因本体数据库的功能术语富集分析和使用京都基因与基因组百科全书数据库的信号通路富集分析，确定重叠的DEG主要参与趋化因子相关信号转导，这可能介导肺癌细胞向脑转移。根据PPI网络的拓扑分析，趋化因子配体2、溶菌酶、基质金属蛋白酶 - 2（MMP - 2）、赖氨酰氧化酶（LOX）和颗粒酶B被鉴定为潜在的生物标志物。两个显著的节点，MMP - 2和LOX，出现在PPI网络中，并且是微小RNA - 靶标网络中的关键点，因为它们受hsa - let - 7d调控。在本研究中，许多DEG和微小RNA被视为肺腺癌转移的预后生物标志物。这些DEG主要与趋化因子介导的信号通路相关。此外，MMP - 2和LOX被预测为hsa - let - 7d的靶标。
