Gene microarray expression profile analysis of differentially expressed genes of potential alternative pathways in non–small cell lung cancer: In search of biomarkers

In this study, we aimed to identify genes that could be involved in alternative pathways linked to the pathogenesis of non–small cell lung cancer (NSCLC), which could provide novel molecular biomarkers. Owing to NSCLC subtypes, three individual NSCLC data sets were downloaded and analyzed. Gene–subsetting subsequent meta–analysis was performed to screen differentially expressed genes (DEGs). The functional enrichment and pathway analyses were then executed using comprehensive bioinformatics analysis. Accordingly, the three hub genes of alternative pathways and their strong correlation with NSCLC pathway were initially identified as potential candidates (common DEGs) for the progression of NSCLC. The clinicopathological functions of common DEGs in NSCLC were validated by analyzing transcription factors targeting common DEGs, and their effectiveness was validated by analysis of protein/gene interactions and biological processes annotations. Finally, elucidated genes, such as protein phosphatase 3 catalytic subunit alpha (PPP3CA) of calcium signaling pathway, ubiquitin conjugating enzyme E2–Q1 (UBE2Q1) of β–catenin–EGFR–PI3K–Akt–mTOR signaling pathway and TATA–Box binding protein like–1 (TBPL1) of RNA polymerase–II transcription initiation and promoter clearance and PI3K–Akt signaling pathway were recognized as alternative networks mostly associated with the progression of NSCLC by co–occurred with oncogenes of the extracellular–signal–regulated kinase (ERK) pathway; and these genes can confer resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in NSCLC therapy through various mechanisms. Together, these results indicate that mutation–activated alternative pathway genes and related checkpoints can confer progression to NSCLC and drug resistance; therefore, which could provide as promising biomarkers for early detection and treatment of NSCLC.