Integrated Network Analysis Reveals FOXM1 and MYBL2 as Key Regulators of Cell Proliferation in Non-small Cell Lung Cancer

Background: Loss of control on cell division is an important factor for the development of non-small cell lung cancer (NSCLC), however, its molecular mechanism and gene regulatory network are not clearly understood. This study utilized the systems bioinformatics approach to reveal the “driver-network” involve in tumorigenic processes in NSCLC. Methods: A meta-analysis of gene expression data of NSCLC was integrated with protein-protein interaction (PPI) data to construct an NSCLC network. MCODE and iRegulone were used to identify the local clusters and its upstream transcription regulators involve in NSCLC. Pair-wise gene expression correlation was performed using GEPIA. The survival analysis was performed by the Kaplan-Meier plot. Results: This study identified a local “driver-network” with highest MCODE score having 26 up-regulated genes involved in the process of cell proliferation in NSCLC. Interestingly, the “driver-network” is under the regulation of TFs FOXM1 and MYBL2 as well as miRNAs. Furthermore, the overexpression of member genes in “driver-network” and the TFs are associated with poor overall survival (OS) in NSCLC patients. Conclusion: This study identified a local “driver-network” and its upstream regulators responsible for the cell proliferation in NSCLC, which could be promising biomarkers and therapeutic targets for NSCLC treatment.