Investigation into the underlying molecular mechanisms of non-small cell lung cancer using bioinformatics analysis

Abstract

Development of new therapeutic strategies has proven to be of little impact on non-small cell lung cancer (NSCLC), and unfortunately, its molecular mechanisms still remain poorly understood. Therefore, the current study aimed to diagnose the genes associated in the pathogenesis of NSCLC. The differentially expressed genes (DEGs) were diagnosed using the limma software package. The WebGestalt was used to perform pathway and Gene Ontology (GO) enrichment analysis of the DEGs. Protein-protein interaction (PPI) networks, extracted modules, miRNA-target genes regulatory network and miRNA-target genes regulatory network were used to obtain insight into the actions of DEGs. Survival analysis for DEGs carried out. A total of 118 DEGs, including 74 up-regulated and 44 down-regulated genes were diagnosed between serum starved Calu-6 lung cancer cells transfected with control siRNA and serum starved Calu-6 lung cancer cells transfected with siRNA against the LAPTM4B gene. The up-regulated genes were enriched in PPAR signalling pathway, angiogenesis, positive regulation of neuron projection development and extracellular space. The down-regulated genes were enriched in FoxO signalling pathway, plasminogen activating cascade, cardiac chamber morphogenesis and cell surface. The current study screened the genes in PPI network, extracted modules, miRNA-target genes regulatory network and TF-target genes regulatory network with higher degrees as hub genes, which included FGFR1, HEY1, SPP1, FOS, NDRG1, TFF3, CDK15, PDGFRB, IL7R, LYPD6B, IQGAP2, CEACAM1, VEGFA, SGK1, GPRC5B and WNT5A. Survival and expression analysis suggested that low expressed CACNA1C and GATA2, and high expressed MANSC1 and MSX2 in patients with NCSLC was linked with a positive prognosis for overall survival and all individual stages of NSCLC. In conclusion, the current study diagnosed DEGs between serum starved Calu-6 lung cancer cells transfected with control siRNA and serum starved Calu-6 lung cancer cells transfected with siRNA against the LAPTM4B gene, which could improve our understanding of the molecular mechanisms of small interference RNA (siRNA) against LAPTM4B in NSCLC, and up- and down-regulated genes, over and under expressed genes in NSCLC patients indicated a positive prognosis for overall survival and may be used as a prognostic biomarker for patients with NSCLC. Thus, we developed a signature based on seven DEGs with prognostic value for NSCLC patients using multi-steps bioinformatics methods, which may provide new insights and potential biomarkers for prognosis, as well as possibly serving as new therapeutic targets in clinical applications.