Focal Adhesion Related Gene Signature for Glioma: The Pivotal Role of RAP1B in Disease Progression

Introduction: Gliomas are the most common malignant primary brain tumors in adults, with generally unfavorable outcomes. Although focal adhesion-related genes are implicated in glioma progression, their clinical applicability remains limited. Methods: mRNA expression profiles were analyzed in 938 glioma samples from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA), with TCGA as the discovery cohort and CGGA as the validation cohort. Consensus clustering and LASSO Cox regression were used to construct a focal adhesion-related gene (FARG) signature. Survival analysis, pathway enrichment, immune infiltration, and drug response analyses were subsequently performed based on this signature. In vitro and in vivo assays were performed to investigate RAP1B, the gene with the highest coefficient in the FARG signature. Results: A 9-gene FARG signature was identified and effectively stratified patients into high- and low-risk groups with significantly different outcomes. High-risk patients exhibited malignant molecular features, activation of oncogenic pathways, treatment resistance, and an immunosuppressive microenvironment. RAP1B contributed most to the risk score, was significantly upregulated in gliomas, and correlated with poor prognosis. Mechanistically, NFKB1 enhanced RAP1B transcription, promoting glioma proliferation, migration, and tumorigenesis. Discussion: The FARG signature integrates molecular and immune characteristics of gliomas, offering a predictive model for patient prognosis. RAP1B, as a key molecular target, holds potential for improving patient survival. However, this study largely relies on public databases, and further validation in independent cohorts and functional models is required. conclusion: We report a novel FARG signature that shows promising survival prediction and treatment guidance for glioma patients, and confirm RAP1B's oncogenic role. Conclusion: This study establishes a FARG-based prognostic model and identifies RAP1B as a potential therapeutic target in glioma.