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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.

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