RAC1 as a potential pan-cancer diagnostic, prognostic, and immunological biomarker

Ras-related C3 botulinum toxin substrate 1 (RAC1) is an important member of the Rho GTPase family involved in tumorigenesis. However, its role and potential clinical utility across cancer entities in solid tumors is unknown.

We analyzed data from various databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project, cBioPortal, Tumor Immune Estimation Resource 2 (TIMER2), and published articles. A prognostic nomogram for liver hepatocellular carcinoma (LIHC) patients was developed based on RAC1-guanosine triphosphate (GTP) gene expression levels, which were validated using immunohistochemistry (IHC).

In this study, RAC1 was highly expressed in most cancers and correlated with prognosis and pathological stages. Furthermore, significant associations were observed between RAC1 and DNA methylation, immune cell infiltration, immune-related genes, tumor mutational burden, and microsatellite instability in most tumors. As a use case, we employed gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) to analyze the biologic importance of RAC1 expression and established a prognostic nomogram based on tumor stage and RAC1 expression, which can better predict the overall survival rate of patients with LIHC better than tumor stage alone. The gene expression results were validated with IHC, which confirmed a higher expression of the RAC1-GTP protein in LIHC compared to paracancerous tissues.

This extensive solid tumor analysis provides sound evidence that RAC1 can serve as both as an immunotherapy target and as a diagnostic and prognostic biomarker.