Finding and Analyzing New Target Genes for Treatment of Lung Adenocarcinoma using Bioinformatics

Overview

Lung adenocarcinoma (LUAD) accounts for forty percent of all lung cancer cases in the United States. Treatment currently focuses on surgery and chemotherapy, but survival rates remain lower than fifteen percent. The purpose of this investigation is to use an integrated bioinformatics approach to identify key mutated genes in LUAD that are differentially expressed, environmentally responsive, functionally important, and affect survival rates in patients. First, a total of 23,483 genes, from nine cancer databases and published studies, were identified as either differentially expressed, mutated, or environmentally responsive. There were 107 genes common to all 9 sources that served as the curated list for further analysis. The Database for Annotation, Visualization and Integrated Discovery showed that many of the 107 genes were significantly involved in common oncogenetic processes and pathways, such as DNA replication, DNA repair, ATP binding, and pathways in specific cancers. This supports a large involvement in the development of cancer, and thus the genes serving as potential targets. Among the 107 genes, the Comparative Toxicogenomics Database found 38,532 gene-environment interactions. Each of the chemicals can be used as a treatment by altering the genes’ expression, genetic sequence, and effect on the cell. Next, a protein-to-protein interaction network was mapped with the Search Tool for the Retrieval of Interacting Genes/Proteins. This revealed 1116 protein-to-protein interactions among the 107 genes, 25 of which had more than 30 interactions each. This demonstrates a large interconnectedness between the set of genes meaning that a change in one change, may have an effect on other genes and thus on a larger process. Finally, these 25 genes were analyzed with OncoLnc, which resulted in three genes, Checkpoint Kinase 1, Cyclin E1 and Exonuclease 1 (EXO1), that had a significant correlation between increased differential expression in LUAD and worsened patient survival. This supports the claim that all three of these genes serve as oncogenes, genes that transform healthy cells into cancerous cells. Among these, EXO1 has been the least studied in LUAD serving as a potentially novel target for treatment. Information from this study can help identify and understand new targets in gene therapies to serve as preventative and therapeutic measures in cancer treatment. Additionally, the method created by this investigation can be applied to other genetic diseases and disorders to allow for a more a comprehensive understanding of the gene makeup and the development of treatments for various diseases.