BMI-dependent prognostic role of EEF1G in breast cancer: A 15-year follow-up of the Guangzhou Breast Cancer Cohort Study.

OBJECTIVE: Eukaryotic elongation factor 1 gamma (EEF1G) has emerged as a potential prognostic marker in various malignancies. Yet, its association with breast cancer (BC) prognosis, particularly in the context of body mass index (BMI) status, remains unexplored. Therefore, we investigated the prognostic value and role of EEF1G in BC across different BMI categories. METHODS: EEF1G expression was assessed through immunohistochemistry in tissue microarrays on 1011 patients with primary invasive BC. Prognostic effects were analyzed using the Cox proportional hazards regression. GSE78958 dataset downloaded from the Gene Expression Omnibus (GEO) database was used to validate our findings. Gene Set Enrichment Analysis (GSEA) was performed using R packages, and protein-protein interaction (PPI) networks were generated using the STRING database and Cytoscape software. RESULTS: Elevated EEF1G expression was associated with a better prognosis in patients with BMI ≤ 24 kg/m(2) (hazard ratio (HR) for overall mortality = 0.67, 95% confidence interval (CI): 0.43-1.03; HR for progression = 0.60, 95% CI: 0.42-0.86). In contrast, for patients with BMI > 24 kg/m(2), it appeared to be associated with poorer outcomes (HR for overall mortality = 1.74, 95% CI: 0.96-3.17; HR for progression = 1.63, 95% CI: 1.00-2.66). In patients with BMI > 24 kg/m(2), EEF1G was associated with specific metabolic and oncogenic pathways, which were not statistically significant in patients with BMI ≤ 24 kg/m(2). The top interacting genes with EEF1G differed between the BMI categories. CONCLUSIONS: This study showed EEF1G expression was inversely associated with BC prognosis in different BMI categories, indicating its potential as a prognostic marker and therapeutic target in BC. The differential effects underscore the need for personalized approaches in BC management and research.