Analyzing Integrated Network of Methylation and Gene Expression Profiles in Lung Squamous Cell Carcinoma

Abstract

Gene expression, DNA methylation, and their organizational relationships are commonly altered in lung squamous cell carcinoma (LUSC). To elucidate these complex interactions, we reconstructed a differentially expressed genes (DEGs) network and differentially methylated cytosine (DMCs) network by partial information decomposition and inverse correlation algorithm, respectively. Then, we performed graph union to integrate the networks. The community detection and enrichment analysis of the integrated network revealed the tight interaction between the gene sets of the cell cycle, keratinization, immune system, and xenobiotic metabolism in LUSC. The DMCs analysis showed that the hypomethylation targeted the gene sets that were responsible for cell cycle, keratinization, and NRF2 pathway. In other hand, hypermethylated genes affected the circulatory system development, immune system, extracellular matrix organization, and cilium organization. By centrality measurement, we detected NCAPG2, PSMG3, and FADD as hub genes which were highly connected to other nodes and might play important roles in LUSC gene dysregulation. We also found that the high betweenness centrality genes affect the patients' survival. These results showed the integrated network analysis enabled us to obtain the global view of the interactions and regulations in LUSC.