Identification of Hub Genes and Potential Drugs in Neurofibromatosis 1: An Integrated Bioinformatics Analysis
Abstract
Background: Neurofibromatosis Type 1 (NF1) is an autosomal dominant benign tumor predisposition syndrome. Till date very little is known about the pathogenesis and underlying mechanisms of NF1. Objective: The aim of this study is to use integrated bioinformatics approaches to explore the pathways involved in NF1 onset by identifying hub genes and potential drugs. Methods: Microarray profiling datasets were used to obtain Differentially Expressed Genes (DEGs) by analyzing in GEO2R. 1730 DEGs were found and STRING analysis revealed Protein-Protein Interaction (PPI) network of these DEGs. Molecular Complex was detected using MCODE plugin of Cytoscape. CytoHubba plugin of Cytoscape was used to declare hub genes based on their degree of connectivity. Lastly, Drug-Gene Interaction Database (DGIdb) and Gene Expression Profiling Interactive Analysis (GEPIA) servers were used to find potential drugs and survival analysis of hub gene, respectively. Results: Degree of connectivity revealed 10 hub genes out of 1730 DEGs. The survival analysis of these hub genes resulted in three specific genes that are altered in NF1 patients. These three genes are named as BRCA1, KIF11 and LAMA1. Furthermore, 13 potential drugs were also predicted to influence BRCA1, KIF11 and LAMA1 and have therapeutic potential against NF1. Conclusion: This research opens ways to understanding the pathogenesis of NF1. All three genes are key biological markers and potential drug targets that can be confirmed by further experiments. Moreover, 13 potential drugs were found to work against the disease.