• Zhibo Shao, Hengyu Ren, Xuliren Wang, Qi Zhang, Jingyan Xue, Yayun Chi, Bingqiu Xiu, and Jiong Wu.
• Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
• Int J Med Sci. 2025 Jan 1; 22 (3): 662679662-679.

AbstractRAC1, a member of the Rho family GTPases, has been implicated in various cancers, yet its pan-cancer landscape and role in the tumor immune microenvironment remain underexplored. This study presents a comprehensive analysis of RAC1 across 33 cancer types, revealing its high expression in a broad range of cancers and its association with poor prognosis. RAC1 expression correlates with genomic alterations, including CNVs, TMB, and MSI. RAC1 knockdown reduces cell proliferation and metastasis in breast and lung cancer cells, suggesting its oncogenic potential. Notably, RAC1 is negatively correlated with B cell infiltration, indicating its role in regulating the immune microenvironment. Functional enrichment analysis showed that high RAC1 expression is linked to lower enrichment in B cell activation and immune response pathways. Single-cell transcriptome analysis identified RAC1 expression primarily in epithelial cells, associated with tumor progression, and spatial transcriptome analysis showed a mutually exclusive co-localization between B cell infiltration regions and RAC1-expressing epithelial cells. Based on RAC1 expression and B cell interaction, a prognostic signature was established to predict prognosis at the pan-cancer level.© The author(s).

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