Sun Ruiying, Meng Xia, Wang Wei, Liu Boxuan, Lv Xin, Yuan Jingyan, Zeng Lizhong, Chen Yang, Yuan Bo, Yang Shuanying
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Oncol Lett. 2019 Aug;18(2):1723-1732. doi: 10.3892/ol.2019.10498. Epub 2019 Jun 19.
Lung cancer is one of the most common types of malignancy worldwide. The prognosis of lung cancer is poor, due to the onset of metastases. The aim of the present study was to examine lung cancer metastasis-associated genes. To identify novel metastasis-associated targets, our previous study detected the differentially expressed mRNAs and long non-coding RNAs between the large-cell lung cancer high-metastatic 95D cell line and the low-metastatic 95C cell line by microarray assay. In the present study, these differentially expressed genes (DEGs) were analyzed via bioinformatics methods, including Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. A protein-protein interaction network was subsequently constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins online database and Cytoscape software, and 17 hub genes were screened out on the basis of connectivity degree. These hub genes were further validated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) using the online Gene Expression Profiling Interactive Analysis database. A total of seven hub genes were identified to be significantly differentially expressed in LUAD and LUSC. The prognostic information was detected using Kaplan-Meier plotter. As a result, five genes were revealed to be closely associated with the overall survival time of patients with lung cancer, including phosphoinositide-3-kinase regulatory subunit 1, FYN, thrombospondin 1, nonerythrocytic α-spectrin 1 and secreted phosphoprotein 1. In addition, lung cancer and adjacent lung tissue samples were used to validate these hub genes by reverse transcription-quantitative polymerase chain reaction. In conclusion, the results of the present study may provide novel metastasis-associated therapeutic strategies or potential biomarkers in non-small cell lung cancer.
肺癌是全球最常见的恶性肿瘤类型之一。由于转移的发生,肺癌的预后较差。本研究的目的是检测与肺癌转移相关的基因。为了确定新的转移相关靶点,我们之前的研究通过微阵列分析检测了大细胞肺癌高转移95D细胞系和低转移95C细胞系之间差异表达的mRNA和长链非编码RNA。在本研究中,通过生物信息学方法对这些差异表达基因(DEGs)进行了分析,包括基因本体功能分析和京都基因与基因组百科全书通路富集分析。随后使用在线检索相互作用基因/蛋白质的搜索工具数据库和Cytoscape软件构建了蛋白质-蛋白质相互作用网络,并根据连接度筛选出17个枢纽基因。使用在线基因表达谱交互式分析数据库在肺腺癌(LUAD)和肺鳞状细胞癌(LUSC)中进一步验证了这些枢纽基因。共鉴定出7个枢纽基因在LUAD和LUSC中存在显著差异表达。使用Kaplan-Meier绘图仪检测预后信息。结果显示,5个基因与肺癌患者的总生存时间密切相关,包括磷酸肌醇-3-激酶调节亚基1、FYN、血小板反应蛋白1、非红细胞α-血影蛋白1和分泌性磷蛋白1。此外,通过逆转录定量聚合酶链反应,使用肺癌及癌旁肺组织样本对这些枢纽基因进行了验证。总之,本研究结果可能为非小细胞肺癌提供新的转移相关治疗策略或潜在生物标志物。