High expression of G3BP1 is associated with poor prognosis in breast invasive carcinoma

Breast invasive carcinoma (BRCA) is the most common type of cancer affecting women worldwide. Biomarkers such as estrogen receptor, progesterone receptor and HER2 are currently utilized in clinical practice for breast cancer diagnosis; yet their sensitivity and specificity remain limited. However, Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1), an RNA-binding protein, has been implicated in tumor progression in various cancers, yet its clinical relevance and mechanistic role in BRCA still remain unclear. The present study integrated multi-omics data analysis and experimental validation to address this. G3BP1 mRNA and protein expression levels in BRCA were analyzed using The Cancer Genome Atlas, Tumor Immune Estimation Resource (TIMER) and Clinical Proteomic Tumor Analysis Consortium databases. Kaplan-Meier survival analysis and Cox regression were employed to evaluate the prognostic value of G3BP1. Gene set enrichment analysis (GSEA) was performed to identify associated signaling pathways and immune cell infiltration correlations were assessed using CIBERSORT and TIMER. Additionally, 38 samples of BRCA and adjacent normal tissue were collected for immunohistochemical (IHC) validation and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curves. G3BP1 was significantly upregulated in BRCA tissues at both mRNA and protein levels (P<0.05). High G3BP1 expression was associated with the advanced cancer lymph node stage (P=0.005) and a poor prognosis [overall survival, disease-free survival (DFS), distant metastasis-free survival and post-progression survival; all P<0.05]. Differential gene analysis identified 67 upregulated and 9 downregulated genes. GSEA revealed G3BP1 enrichment in key pathways such as PI3K/AKT/mTOR signaling and ubiquitin-mediated proteolysis. Immune analysis showed a significant positive association between G3BP1 and M2 macrophage infiltration (P<0.05) and a significant negative association between G3BP1 and CD8⁺ T cells (P<0.05). IHC confirmed higher G3BP1 expression in BRCA compared with normal tissues (P<0.001), with an area under the ROC curve (AUC) of 0.777 and a 5-year DFS prediction AUC of 0.730. The present findings indicate that G3BP1 is a potential independent prognostic biomarker for BRCA. Its upregulation promotes tumor progression by activating the PI3K/AKT/mTOR signaling pathway and modulating the tumor immune microenvironment. These findings provide a theoretical foundation for targeting G3BP1 in BRCA diagnosis and immunotherapy.