Identification of Hub Genes Associated with Development of Lung Adenocarcinoma by Integrated Bioinformatics Analysis

Abstract

Purpose: Lung adenocarcinoma (LUAD) has high heterogeneity and poor prognosis, posing a major challenge to human health worldwide. Therefore, it is necessary to improve our understanding of the molecular mechanism of LUAD in order to be able to better predict its prognosis and develop new therapeutic strategies for target genes.Methods: The Cancer Genome Atlas and Gene Expression Omnibus, were selected to comprehensively analyze and explore the differences between LUAD tumors and adjacent normal tissues. Critical gene information was obtained through weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and survival analysis.Results: Using WGCNA and differential gene expression analysis, 29 differentially expressed genes were screened. The functional annotation analysis showed these genes to be mainly concentrated in heart trabecula formation, regulation of inflammatory response, collagen-containing extracellular matrix, and metalloendopeptidase inhibitor activity. Also, in the protein–protein interaction network analysis, 10 central genes were identified using Cytoscape's CytoHubba plug-in. The expression of CDH5, TEK, TIMP3, EDNRB, EPAS1, MYL9, SPARCL1, KLF4, and TGFBR3 in LUAD tissue was found to be lower than that in the normal control group, while the expression of MMP1 in LUAD tissue was higher than that in the normal control group. According to survival analysis, the low expression of MYL9 and SPARCL1 was correlated with poor overall survival in patients with LUAD. Finally, through the verification of the Oncomine database, it was found that the expression levels of MYL9 and SPARCL1 were consistent with the mRNA levels in LUAD samples, and both were downregulated.Conclusion: Two survival-related genes, MYL9 and SPARCL1, were determined to be highly correlated with the development of LUAD. Both may play an essential role in the development LUAD and may be potential biomarkers for its diagnosis and treatment in the future.