A prognostic gene signature based on focal adhesion related genes for gliomas and identification of the role of RAP1B in glioma progression

Abstract

Background The most common malignant primary brain tumor in adults is the gliomas, characterized by extremely variable overall survival (OS) for patients. Although it has been found that focal adhesion genes are associated with clinical prognosis in glioma patients, this marker is rarely used clinically. Methods We systematically characterized mRNA expression of focal adhesion related genes in gliomas and explored their expression signature based on 938 samples from TCGA dataset and CGGA dataset. Glioma samples were clustered using mRNA expression of focal adhesion genes using an unsupervised clustering method. Subsequently, based on prognosis-associated genes, the focal adhesion related gene signature (FARGS) was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression. Additionally, multiple bioinformatics methods were used to examine the value of FARGS in predicting patient outcomes, clinical features, oncogenic pathways, tumor immune microenvironment and drug response. Furthermore, in vitro and in vivo experiments were conducted to validate the role of RAP1B in U87 glioma cells. Results According to LASSO Cox regression analysis, a 9-FARG signature was found to be strongly linked with OS in glioma patients, characterized by a high-risk and a low-risk score pattern. The FARGS was found to be tightly linked with malignant molecular biomarkers, including IDH wild-type, unmethylated MGMTp, and non-codeletion of 1p19q. Furthermore, the high-risk group exhibited an enrichment of multiple oncogenic biological pathways. Interestingly, the results presented that the FARGS has a strong association with therapeutic response and tumor immunosuppressive microenvironment in gliomas, including immune infiltrations of M2-type macrophages, MDSCs and Tregs, and elevated immunosuppressors’ mRNA expression. Lastly, the oncogenic role of RAP1B in U87 glioma cells was also functionally confirmed. Conclusions In conclusion, we reported a novel FARGS with promising survival prediction for glioma patients, as well as confirmation of RAP1B's oncogenic role.