Hub genes and key pathways of non-small lung cancer identified using bioinformatics

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for ~80% of all lung cancer cases. The aim of the present study was to identify key genes and pathways in NSCLC, in order to improve understanding of the mechanism of lung cancer. The GSE33532 gene expression dataset, containing 20 normal and 80 NSCLC samples, was used. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to obtain the enrichment data of differently expressed genes (DEGs). Disease modules within NSCLC were constructed by Cytoscape, using protein-protein interaction (PPI) from the Search Tool for the Retrieval of Interacting Genes database. In addition, the Kaplan Meier plotter KMplot was used to assess the top hub genes in the PPI network. As a result, 1,795 genes were identified in NSCLC; 729 were upregulated and 1,066 were downregulated. The results of the GO analysis indicated that the upregulated DEGs were significantly enriched in 'biological processes' (BP), including 'cell cycle and nuclear division'; the downregulated DEGs were also significantly enriched in BP, including 'response to wounding', 'anatomical structure morphogenesis' and 'response to stimulus'. Upregulated DEGs were also enriched in 'cell cycle', 'DNA replication' and the 'tumor protein 53 signaling pathway', while the downregulated DEGs were also enriched in 'complement and coagulation cascades', 'malaria' and 'cell adhesion molecules'. The top 9 hub genes were cyclin-dependent kinase 9 (CDK1), polo-like kinase 1, aurora kinase B, cell division cycle 20, baculoviral initiator of apoptosis repeat containing 5, mitotic checkpoint serine/threonine kinase B, proliferating cell nuclear antigen (PCNA), centromere protein A and MAD2 mitotic arrest deficient-like 1, and the KMplot results revealed that the high expression levels of these genes resulted in significantly low survival rates, compared with low expression samples (P<0.05), with the exception of PCNA and CDK1. In the pathway crosstalk analysis, 26 nodes and 41 interactions were divided into two groups: One module of the two groups primarily included 'metabolism of amino acid' and the other primarily contained 'tumor necrosis signaling' pathways. In conclusion, the present study assisted in improving the understanding of the molecular mechanisms underlying NSCLC development, and the results may help the understanding of the biological mechanism of NSCLC.

Keywords: different expression; enrichment; microarray; non-small cell lung cancer; pathway.

Figure 1.

Heat map of the top 100 differentially expressed genes (top 50 upregulated and top 50 downregulated genes). Yellow denotes upregulation and red represents downregulation. The blue and red bar represents control and case group, respectively.

Figure 2.

Volcano plot of the distribution of all differentially expressed genes, mapping the 729 upregulated genes (red crosses) and 1,066 downregulated genes (blue triangles). FC, fold change.

Figure 3.

Top 5 modules from the high-score protein-protein interactive network. (A-E) Modules 1–5 and their enriched pathways. FDR, false discovery rate.

Figure 4.

Pathway crosstalk among differentially expressed genes-enriched pathways. AGE-RAGE, advanced glycation endproducts-receptor for AGE; ECM, extracellular matrix; p53, tumor protein 53; TNF, tumor necrosis factor.

Figure 5.

Survival analysis of hub genes. (A) PLK, (B) AURKB, (C) CDC20, (D) BIRC5, (E) BUB1B, (F) CENPA and (G) MAD2L1 expression indicated significantly lower survival rates, compared with low expression samples. (H) PCNA expression did not exhibit a significantly different survival rates. PLK, polo-like kinase 1; AURKB, aurora kinase B; CDC20, cell division cycle 20; BIRC5, baculoviral initiator of apoptosis repeat containing 5; BUB1B, BUB1 mitotic checkpoint serine/threonine kinase B; CENPA, centromere protein A; MAD2L1, MAD2 mitotic arrest deficient-like 1; PCNA, proliferating cell nuclear antigen.