AUTHOR=Ahmed Firoz 

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

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01011

DOI=10.3389/fonc.2019.01011

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> A meta-analysis of gene expression data of NSCLC was integrated with protein-protein interaction (PPI) data to construct an <italic>NSCLC network</italic>. 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.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusion:</bold> 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.</p>