Integrated Pan-Cancer Profiling of RAC1: Prognostic, Immunomodulatory, and Therapeutic Resistance Insights

Abstract RAC1, a member of the Rho family GTPases, has been implicated in various cancer types, but its pan-cancer landscape and clinical significance remain underexplored. In this study, we conducted a comprehensive analysis of RAC1 expression, its correlation with clinical outcomes, and its role in the tumour microenvironment across 33 cancer types. Our findings revealed that RAC1 is highly expressed in a broad range of cancers and is associated with poor prognosis. RAC1 expression was found to be significantly linked to genomic alterations, including copy number variations (CNVs), tumour mutational burden (TMB), and microsatellite instability (MSI). Moreover, RAC1 was negatively correlated with B cell infiltration, suggesting its potential role in shaping a "cold" tumour microenvironment. Functional enrichment analysis indicated that RAC1 is involved in pathways related to B cell activation and immune response. Loss-of-function experiments demonstrated that RAC1 knockdown reduces cell proliferation in breast and lung cancer cells, in vivo and in vitro, suggesting its oncogenic potential. Single-cell analysis uncovered that RAC1 predominantly exerts its influence within epithelial cells. This pan-cancer analysis provides a detailed understanding of RAC1's role in cancer progression and its potential as a prognostic biomarker and therapeutic target for immunotherapy.