AURKA, TOP2A and MELK are the key genes identified by WGCNA for the pathogenesis of lung adenocarcinoma

Abstract

The comprehensive analysis of single or multiple microarray datasets is currently available in Gene Expression Omnibus (GEO) databases, with several studies having identified genes strongly associated with the development of lung adenocarcinoma (LUAD). However, the mechanisms of LUAD development remain largely unknown and has not yet been systematically studied; thus, further studies are required in this field. In the present study, weighted gene co‑expression network analysis (WGCNA) was used for the evaluation of key genes with potential high risk of LUAD, and to provide more reliable evidence concerning its pathogenesis. The GSE140797 dataset from the high‑throughput GEO database was down‑ loaded and was first analyzed using the Limma package in the R language in order to determine the differentially expressed genes. The dataset was then analyzed using the WGCNA package to analyze the co‑expressed genes, and the modular genes with the highest correlation with the clinical phenotype were identified. Subsequently, the pathogenic genes shared in common between the result of the two analyses were imported into the STRING database for protein‑protein interaction network analysis. The hub genes were screened out using Cytoscape, and then The Cancer Genome Atlas analysis, receiver operating characteristic analysis and survival analysis were subsequently performed. Finally, the key genes were evaluated using reverse transcription‑quantitative PCR and western blot analysis. Bioinformatics analysis of the GSE140797 dataset revealed eight key genes: AURKA, BUB1, CCNB1, CDK1, MELK, NUSAP1, TOP2A and PBK. Finally, the AURKA, TOP2A and MELK genes were evaluated in samples from patients with lung cancer using WGCNA and RT‑qPCR, western blot analysis experiments, providing basis for further research on the mechanisms of LUAD development and targeted therapy.