Abstract
Lung cancer is one of the most invasive cancers affecting over a million of the population. Non-small cell lung cancer (NSCLC) constitutes up to 85% of all lung cancer cases, and therefore, it is essential to identify predictive biomarkers of NSCLC for therapeutic purposes. Here we use a network theoretical approach to investigate the complex behavior of the NSCLC gene-regulatory interactions. We have used eight NSCLC microarray datasets GSE19188, GSE118370, GSE10072, GSE101929, GSE7670, GSE33532, GSE31547, and GSE31210 and meta-analyzed them to find differentially expressed genes (DEGs) and further constructed a protein–protein interaction (PPI) network. We analyzed its topological properties and identified significant modules of the PPI network using cytoscape network analyzer and MCODE plug-in. From the PPI network, top ten genes of each of the six topological properties like closeness centrality, maximal clique centrality (MCC), Maximum Neighborhood Component (MNC), radiality, EPC (Edge Percolated Component) and bottleneck were considered for key regulator identification. We further compared them with top ten hub genes (those with the highest degrees) to find key regulator (KR) genes. We found that two genes, CDK1 and HSP90AA1, were common in the analysis suggesting a significant regulatory role of CDK1 and HSP90AA1 in non-small cell lung cancer. Our study using a network theoretical approach, as a summary, suggests CDK1 and HSP90AA1 as key regulator genes in complex NSCLC network.
Highlights
Lung Cancer is one of the most invasive cancer types causing more than 1.38 million deaths worldwide [1]
This study revealed two significant genes, CDK1 and HSP90AA1, as key regulators of Non-Small Cell Lung Cancer (NSCLC)
It was found that the expression of both CDK1 and HSP90AA1 were upregulated in NSCLC, and the expression of both genes was validated in LUAD and LUSC cohort independently
Summary
Lung Cancer is one of the most invasive cancer types causing more than 1.38 million deaths worldwide [1]. Non-Small Cell Lung Cancer (NSCLC) is a kind of epithelial lung cancer. This type of cancer occurs mainly among non-smokers [4]. It is more common in women than in men and has a higher probability of occurring in younger people, among other types of lung cancers. It is usually found in the outer parts of the lung; it is likely to be detected before it metastasizes [5]
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