Unravelling hub genes as potential therapeutic targets in lung cancer using integrated transcriptomic meta-analysis and in silico approach

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Smoking has been identified as the main contributing cause of the disease's development. The study aimed to identify the key genes in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), the two major types of LC. Meta-analysis was performed with two datasets GSE74706 and GSE149507 obtained from Gene Expression Omnibus (GEO). Both the datasets comprised samples from cancerous and adjacent non-cancerous tissues. Initially, 633 differentially expressed genes (DEGs) were identified. To understand the underlying molecular mechanism of the identified genes, pathway enrichment, gene ontology (GO) and protein-protein interaction (PPI) analyses were done. A total of 9 hub genes were identified which were subjected to mutation study analysis in LC patients using cBioPortal. These  9 genes (i.e. AURKA, AURKB, KIF23, RACGAP1, KIF2C, KIF20A, CENPE, TPX2 and PRC1) have shown overexpression in LC patients and can be explored as potential candidates for prognostic biomarkers. TPX2 reported a maximum mutation of 4%. This was followed with high throughput screening and docking analysis to identify the potential drug candidates following competitive inhibition of the AURKA-TPX2 complex. Four compounds, CHEMBL431482, CHEMBL2263042, CHEMBL2385714, and CHEMBL1206617 were identified. The results signify that the selected 9 genes can be explored as biomarkers in disease prognosis and targeted therapy. Also, the identified 4 compounds can be further analyzed as promising therapeutic candidates.Communicated by Ramaswamy H. Sarma.