Prediction of Genes Involved in Lung Cancer with a Systems Biology Approach Based on Comprehensive Gene Information

Abstract

Over the past few years, hundreds of genes have been reported in relation to lung cancer. Systems biology studies can help validate this association and find the most valid genes to use in the diagnosis and treatment. We reviewed the candidate genes for lung cancer in 120 published articles from September 1, 1993, to September 1, 2020. We obtained 134 up- and 36 downregulated genes for lung cancer in this article. The genes extracted from the articles were imported to Search Tool for the Retrieval of Interacting genes/proteins (STRING) to construct the protein-protein interaction (PPI) Network and pathway enrichment. GO ontology and Reactome databases were used for describing the genes, average length of survival, and constructing networks. Then, the ClusterONE plugin of Cytoscape software was used to analyze and cluster networks. Hubs and bottleneck nodes were defined based on their degree and betweenness. Common genes between the ClusterONE plugin and network analysis consisted of seven genes (BRCA1-TP53-CASP3-PLK1-VEGFA-MDM2-CCNB1 and PLK1), and two genes (PLK1 and TYMS) were selected as survival factors. Our drug-gene network showed that CASP3, BRCA1, TP53, VEGFA, and MDM2 are common genes that are involved in this network. Also, among the drugs recognized in the drug-gene network, five drugs such as paclitaxel, oxaliplatin, carboplatin, irinotecan, and cisplatin were examined in different studies. It seems that these seven genes, with further studies and confirmatory tests, could be potential markers for lung cancer, especially PLK1 that has a significant effect on the survival of patients. We provide the novel genes into the pathogenesis of lung cancer, and we introduced new potential biomarkers for this malignancy.

Keywords: Biomarkers; Drug targets; Important genes; Lung cancer; Systems biology.