Abstract
Background: Conventionally, RHO GEFs are known as activators for RHO GTPases which promote tumorigenesis. However, the role of RHO GEFs in non-small cell lung cancer (NSCLC) remains largely unknown. Methods: A comprehensive bioinformatics analysis of protein structure, transcriptional expression, survival, methylation, mutation and gene-set enrichment data was performed using multiple databases. Results: Through the screening of 81 RHO GEFs for their expression profiles and correlations with survival, four of them are identified with strong significance for predicting the prognosis of NSCLC patients. The four RHO GEFs, namely ABR, PREX1, DOCK2 and DOCK4, are downregulated in NSCLC compared to normal tissue. The downregulation of ABR, PREX1, DOCK2 and DOCK4, which can be contributed by promoter methylation, is correlated with unfavorable prognosis. Moreover, the underexpression of the four key RHO GEFs upregulates MYC signaling and DNA repair pathways, leading to carcinogenesis and poor prognosis. Conclusions: The data unveil the unprecedented role of ABR, PREX1, DOCK2 and DOCK4 as tumor suppressor in NSCLC. The previously unnoticed functions of RHO GEFs in NSCLC will inspire researchers to investigate the distinct roles of RHO GEFs in cancers, in order to provide critical strategies in clinical practice.
Role of Rho Guanine Nucleotide Exchange Factors in Non-Small Cell Lung Cancer
