Up-regulation of YPEL1 and YPEL5 and down-regulation of ITGA2 in erlotinib-treated EGFR-mutant non-small cell lung cancer: A bioinformatic analysis.

PURPOSE: This study aimed to identify genes with significant alteration following treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs).
METHODS: We downloaded microarray data of GSE67051 from the Gene Expression Omnibus (GEO) database. Genes with differential expression were identified in two groups: erlotinib-treated versus DMSO-treated PC9 cells and erlotinib-treated versus DMSO-treated HCC827 cells. Functional enrichment analysis and protein-protein interaction (PPI) network were performed on the overlapping differentially expressed genes (DEGs). Additionally, miRNAs that can regulate the DEGs were predicted. Small-molecule drugs, with possible synergistic or antagonistic actions with respect to erlotinib, were screened; data validation using another dataset was conducted.
RESULTS: In total, 1466 and 839 DEGs were identified in the aforementioned comparison groups, respectively, among which 267 overlapping up-regulated and 73 down-regulated were observed. The overlapping up- and down-regulated genes were significantly associated with different functions and pathways. ITGA2 had higher centrality scores in the PPI network. Seventy small-molecule drugs, with either possible synergistic or antagonistic roles with erlotinib, were identified. Moreover, up-regulated YPEL1, YPEL2, and YPEL5 were enriched in the miRNA-target regulatory network. Implementing data validation, we found YPEL1, YPEL5, and ITGA2 displayed similar expression profiles in the two datasets.
CONCLUSION: YPEL1 and YPEL5 may be related to the action of erlotinib, and down-regulation of ITGA2 may be associated with the development of acquired resistance to erlotinib in EGFR-mutant NSCLCs. Furthermore, several small-molecule drugs that may have synergistic and antagonistic roles with erlotinib were identified.