Gene expression profiling analysis of lung adenocarcinoma

Abstract

The present study screened potential genes related to lung adenocarcinoma, with the aim of further understanding disease pathogenesis. The GSE2514 dataset including 20 lung adenocarcinoma and 19 adjacent normal tissue samples from 10 patients with lung adenocarcinoma aged 45-73 years was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the two groups were screened using the t-test. Potential gene functions were predicted using functional and pathway enrichment analysis, and protein-protein interaction (PPI) networks obtained from the STRING database were constructed with Cytoscape. Module analysis of PPI networks was performed through MCODE in Cytoscape. In total, 535 upregulated and 465 downregulated DEGs were identified. These included ATP5D, UQCRC2, UQCR11 and genes encoding nicotinamide adenine dinucleotide (NADH), which are mainly associated with mitochondrial ATP synthesis coupled electron transport, and which were enriched in the oxidative phosphorylation pathway. Other DEGs were associated with DNA replication (PRIM1, MCM3, and RNASEH2A), cell surface receptor-linked signal transduction and the enzyme-linked receptor protein signaling pathway (MAPK1, STAT3, RAF1, and JAK1), and regulation of the cytoskeleton and phosphatidylinositol signaling system (PIP5K1B, PIP5K1C, and PIP4K2B). Our findings suggest that DEGs encoding subunits of NADH, PRIM1, MCM3, MAPK1, STAT3, RAF1, and JAK1 might be associated with the development of lung adenocarcinoma.

The Bioenergetic Role of Mitochondria in Lung Cancer

“…Up to 60% of lung adenocarcinoma tissues have a driver mutation. These genes include Kirsten rat sarcoma viral oncogene (KRAS), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and proto-oncogene B-Raf (BRAF) [31,32]. In lung adenocarcinoma, the type of NSCLC most frequently found to plague nonsmokers, smoking causes a very different pathway of tumorigenesis [33].…”

“…Malic enzyme (ME) expression is also significantly increased in the lung tissues of smokers compared to nonsmokers [34]. The EGFR pathway is the most common signaling pathway for lung cancer, and the mutation rate of genes of the EGFR pathway reach 70-80% [32]. About 30-35% of lung adenocarcinoma genetic variation is attributable to the KRAS mutation.…”

“…Mitochondrial respiration genes have also been shown to be upregulated in lung tumor cells. In lung adenocarcinoma, many genes, especially those associated with mitochondrial respiration, have been shown to be differently expressed than in healthy tissue [32]. One study noted 535 upregulated and 465 downregulated differentially expressed genes in lung adenocarcinoma comparing matched tissues of the same patients.…”

“…One prominent class of upregulated genes is related to mitochondrial oxidative phosphorylation and the electron transport chain. ATP5D, UQCRC2, NDUFA2, NDUFB8, NDUFA7, NDUFA1, NDUFB1, NDUFS7, UQCR11, NDUFV1, NDUFV2, and NDUFS3 are specifically related to bioenergetic pathways including mitochondrial ATP synthesis-coupled electron transport and the electron transport chain [32]. Additionally, genes associated with mitochondrial biogenesis are specifically upregulated in circulating lung cancer cells and have been reported to be essential for their metastatic potential [36].…”

Identification of Lung Cancer Related Genes Using Enhanced Floyd Warshall Algorithm in a Protein to Protein Interaction Network

“…Whereas, the most common types of NSCLC are squamous cell carcinoma, large cell carcinoma and adenocarcinoma. In the clinic, approximately 20% of lung cancer patients are diagnosed with SCLC and 80% are diagnosed with NSCLC [3,4]. Hence, the biological behavior of SCLC and NSCLC are significantly different, these two distinct types of lung cancer grow in different ways and also treated differently.…”