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 which influences various traits of cancer such as resistance to therapies. Here we comparatively 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 GSE169513 (for PC9 cells) and GSE123066 (for HCC4006 cells). PPI networks of upregulated mRNAs were obtained based on the STRING database and Cytoscape software. R packages were conducted for enrichment pathway analysis. A total of 7128 and 2812 GR related DEGs were identified in PC9 and HCC4006 cells, respectively. GR related genes mostly influenced cytokine signaling and extracellular matrix organization in PC9 and HCC4006 cells, respectively. The high-expressed hub genes were obtained (19 in PC9 and 16 in HCC4006 GR cells), in which SERPINE1 and CDH2 were overlapped in both GR cell lines. SERPINE1 was also the overlapped hub gene in the transcription regulatory networks of both cell lines based on the TRRUST database. It was found significant correlations between the expression of hub genes and tumor infiltration of cancer-associated fibroblast based on the TIMER2.0 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 tumor microenvironment and may be a new approach for overcoming the GR in LUAD.
