Differentially Expressed mRNAs in Gefitinib Resistance Human Lung Adenocarcinoma Cell Lines: A Bioinformatics Approach

Lung adenocarcinoma (LUAD) is the most common histological subtype of non–small cell lung cancer. Differential gene expression profile of tumors is a crucial event influencing various cancer traits, such as resistance to therapies. We evaluated the mRNA profile, hub genes, and pathways in two gefitinib-resistance (GR) LUAD cell lines. Differentially expressed genes (DEGs) associated with acquired GR were identified from the gene expression profile GSE۱۶۹۵۱۳ (for PC۹ cells) and GSE۱۲۳۰۶۶ (for HCC۴۰۰۶ cells). PPI networks of upregulated mRNAs were obtained based on the STRING database and Cytoscape software. R packages were conducted for enrichment pathway analysis. ۷۱۲۸ and ۲۸۱۲ GR-related DEGs were identified in PC۹ and HCC۴۰۰۶ cells, respectively. GR-related genes influence cytokine signaling and extracellular matrix organization in PC۹ and HCC۴۰۰۶ cells. The high-expressed hub genes were obtained (۱۹ in PC۹ and ۱۶ in HCC۴۰۰۶ GR cells), in which SERPINE۱ and CDH۲ overlapped in both GR cell lines. SERPINE۱ was also the overlapped hub gene in the transcription regulatory networks of both cell lines based on the TRRUST database. Significant correlations between the expression of hub genes and tumor infiltration of cancer-associated fibroblast based on the TIMER۲.۰ database. Overall, two drug resistance cell lines employed different global gene expression alterations. Targeting the upregulated hub genes could restore immune and mechanical abnormalities of the tumor microenvironment and may be a new approach for overcoming the GR in LUAD.

کلیدواژه ها:

Lung adenocarcinoma ، Gefitinib resistance ، mRNA expression profile ، Immune infiltration