Guo Tingting, Ma Hongtao, Zhou Yubai
Department of Biotechnology, College of Life Science & Bioengineering, Beijing University of Technology, Beijing, China.
PeerJ. 2019 Jul 10;7:e7313. doi: 10.7717/peerj.7313. eCollection 2019.
Lung adenocarcinoma (LUAD) is the major subtype of lung cancer and the most lethal malignant disease worldwide. However, the molecular mechanisms underlying LUAD are not fully understood.
Four datasets (GSE118370, GSE85841, GSE43458 and GSE32863) were obtained from the gene expression omnibus (GEO). Identification of differentially expressed genes (DEGs) and functional enrichment analysis were performed using the limma and clusterProfiler packages, respectively. A protein-protein interaction (PPI) network was constructed via Search Tool for the Retrieval of Interacting Genes (STRING) database, and the module analysis was performed by Cytoscape. Then, overall survival analysis was performed using the Kaplan-Meier curve, and prognostic candidate biomarkers were further analyzed using the Oncomine database.
Totally, 349 DEGs were identified, including 275 downregulated and 74 upregulated genes which were significantly enriched in the biological process of extracellular structure organization, leukocyte migration and response to peptide. The mainly enriched pathways were complement and coagulation cascades, malaria and prion diseases. By extracting key modules from the PPI network, 11 hub genes were screened out. Survival analysis showed that except VSIG4, other hub genes may be involved in the development of LUAD, in which MYH10, METTL7A, FCER1G and TMOD1 have not been reported previously to correlated with LUAD. Briefly, novel hub genes identified in this study will help to deepen our understanding of the molecular mechanisms of LUAD carcinogenesis and progression, and to discover candidate targets for early detection and treatment of LUAD.
肺腺癌（LUAD）是肺癌的主要亚型，也是全球最致命的恶性疾病。然而，LUAD潜在的分子机制尚未完全明确。
从基因表达综合数据库（GEO）中获取了四个数据集（GSE118370、GSE85841、GSE43458和GSE32863）。分别使用limma和clusterProfiler软件包进行差异表达基因（DEG）的鉴定和功能富集分析。通过搜索相互作用基因的工具（STRING）数据库构建蛋白质-蛋白质相互作用（PPI）网络，并使用Cytoscape进行模块分析。然后，使用Kaplan-Meier曲线进行总生存分析，并使用Oncomine数据库进一步分析预后候选生物标志物。
共鉴定出349个DEG，包括275个下调基因和74个上调基因，这些基因在细胞外结构组织、白细胞迁移和对肽的反应等生物学过程中显著富集。主要富集的通路有补体和凝血级联反应、疟疾和朊病毒病。通过从PPI网络中提取关键模块，筛选出11个枢纽基因。生存分析表明，除VSIG4外，其他枢纽基因可能参与LUAD的发生发展，其中MYH10、METTL7A、FCER1G和TMOD1此前尚未报道与LUAD相关。简而言之，本研究中鉴定出的新型枢纽基因将有助于加深我们对LUAD致癌和进展分子机制的理解，并发现LUAD早期检测和治疗的候选靶点。
