Integration of PPI network and identification of hub genes

As an online database, the Search Tool for the Retrieval of Interacting Genes (STRING) [12] (version 10.0, http://string-db.org) was use to retrieve gene interactions providing experimental and predictive PPI (protein-protein interaction) information. Cytoscape software (version 3.4.0, http://www.cytoscape.org) was utilized to construct PPI networks [13] to visualize the interaction of the DEGs. Subsequently, the CytoHubba plug-in [14] software was used to calculate the degree centrality of the nodes and hub proteins with higher degrees of centrality were identified [15]. Additionally, the KEGG pathway enrichment analysis of the nodes in the significant modules was performed using Multifaceted Analysis Tool for Human Transcriptome [16].