Emerging roles of the Hippo signaling pathway in non-small cell lung cancer: An In Silico study

Introduction & Objectives: Non-small cell lung cancer (NSCLC) is identified as one of the most important causes of cancer-related mortality. The pathophysiology of NSCLC is complicated and different signaling pathways are associated with NSCLC tumor progression. It has been shown that dysregulations of the Hippo pathway are associated with cell overgrowth and tumorigenesis. In this study, we highlight the Hippo pathway role in NSCLC to find out dysregulated effectors and candidate drug targets for new treatment strategies.Materials & Methods: Microarray data of lung cancer tissues and normal samples were obtained from GSE10799. The screening of gene expression profile was accomplished to reach an evaluation of the data quality and extraction of differentially expressed genes (DEGs) between cancer and normal tissues using TAC software. Furthermore, a protein-protein interaction (PPI) network was constructed to determine the hub genes key modules using STRING and Cytoscape software.Results: A total of 18 DEGs out of 1,597 DEGs were recognized as Hippo pathway core components based on biological processes of KEGG. The PPI network of Hippo pathway core components was sorted and identified, which are mainly classified as cell-cell adhesion, positive regulation of vasculature development, angiogenesis, protein kinase activity and focal adhesion proteins. ITGA1, ITGA8, ITGB1, PPP1R14A, PTK2, CTGF, CDH3, CDH5, CDH6, CDH19, PLCB4, TEK, and FGFR4 were also identified as regulatory nodes of Hippo pathway. Furthermore, Expression and survival analysis were conducted in order to screen and validate key genes. TEK, LIPD, CTGF, CDH5, and ITGA8 were identified as regulatory components of the Hippo pathway in NSCLC.Conclusion: In conclusion, the present study provides new insights into the regulatory mechanisms of the Hippo pathway in NSCLC. Identification of hub genes as novel players in NSCLC may be reflected as potential new targets to improve the low survival rate in NSCLC patients.

کلیدواژه ها:

Non-small cell lung cancer (NSCLC) ، Hippo pathway ، Microarray ، PPI network