Identification of potential key genes and enriched pathways in lung adenocarcinoma via integrated bioinformatics analysis

Lung adenocarcinoma (LUAD), the most common type of non-small cell lung cancer, is still the leading cause of cancer-related deaths worldwide. Adenocarcinoma of the lung represents about ۴۰% of all lung cancers. Many biomarkers and molecular targets have been discovered for prognosis and treatment of LUAD. However, prognosis remains relatively poor and there is still an urgent need to identify new biomarkers and therapies. This study aimed to identify potential key genes and enriched pathways associated with the pathogenesis and prognosis of LUAD. Methods: The gene expression profiles of GSE۷۶۷۰ were selected from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were obtained by the R Bioconductor packages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Protein-protein interaction (PPI) network was established by STRING and visualized by Cytoscape software. Survival analysis was conducted to evaluate the prognostic value of hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was involved in correlating key gene expression with the pathological stage. In addition, we used the online Kaplan–Meier plotter survival analysis tool to evaluate the prognostic value of hub gene expression. Results: In total, ۷۶۰ DEGs were identified, including ۴۷۹ up-regulated genes and ۲۸۱ down-regulated genes. DEGs were mainly enriched in biological processes related to extracellular structure and matrix organizations, and External Encapsulating Structure Organization. KEGG pathways analysis showed that the DEGs were mainly enriched in protein digestion and absorption, viral protein interaction with cytokine and cytokine receptor, and IL-۱۷ signaling pathway. With the threshold of degree≥۷, and ۰.۰۰۵≤betweeness≤۱ ۱۰۷ genes were found. A PPI network of these genes was constructed, consisting of ۱۱۶ nodes and ۲۳۹۸ edges. Ten genes(CDK۱, CCNA۲, CCNB۱, CDC۲۰, BUB۱B, CCNB۲, PLK۱, UBE۲C, CEP۵۵, NCAPG) were considered as hub genes owing to high degrees in the network. From our findings, the role of ۲ genes (PRF۱, and SERPING۱) had not been studied enough in lung adenocarcinoma and could be further studied. GEPIA analysis showed that hub genes were abnormally expressed in LUAD as compared to normal lung tissue. In addition, survival analysis indicated that increased expression of hub genes was associated with poor prognosis. Conclusion: In conclusion, the present study indicates that the identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of LUAD, and may be used as molecular targets and diagnostic biomarkers for the treatment of LUAD.

کلیدواژه ها:

lung adenocarcinoma ، bioinformatics ، survival analysis ، gene expression ، biomarker