Background
Lung cancer (LUCA) is the leading cause of cancer-related morbidities and mortalities globally. Despite the recent advancements in lung cancer research, understanding of the molecular mechanism underlying LUCA tumorigenesis and prognosis remains suboptimal. This study aims to identify the candidate biomarkers and therapeutic genes in lung cancer.
Methods
In this study, gene expression profiles of GSE30219, GSE33532, GSE32863 and GSE43458 were downloaded from GEO. The differentially expressed genes (DEGs) in LUAD tissue and normal lung tissue with a p-value < 0.05 and a |log fold change (FC)| >1.0 were identified by GEO2R. For functional enrichment analysis of these DEGs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed with KOBAS and DAVID tools. Next, the candidate hub genes were filtered out with Cytoscape using CytoHubba plugin. These hub genes were validated by (the Cancer Genome Atlas) TCGA-based gene expression analysis, protein-protein network interaction (PPI) analysis, survival analysis. Moreover, the expression of these genes in cancer and normal tissue was assessed in the Human Protein Atlas (HPA) database. In addition, miRNA network of the hub genes was constructed. Finally, DGIdb database was used to check the drug-targeting potentials of the hub genes.
Results
a total of 332 overlapping differentially expressed genes (DEGs) including 73 upregulated and 259 downregulated, respectively were identified. GO analysis revealed that the DEGs were principally regulating various cancer-associated functions and pathways. The module analysis revealed 55 hub genes in 4 modules. The survival analysis through Kaplan-Meier (KM) plotter indicated that the altered expression of these genes resulted in the poor overall survival (OS) of LUCA patients. Moreover, these genes show a differential expression on both protein and mRNA level in cancer patient compared to the normal. In addition, in addition, 6 potential microRNAs (miRNAs) interacting with hub genes were identified. Finally, a list of 117 therapeutic small molecules was tabulated that could facilitate LUCA treatment.
Conclusions
the findings of this study may help in the development of novel and reliable biomarkers for diagnosis, prognosis and therapeutic intervention for LUAD.