Abstract
BACKGROUND: Breast cancer (BC) is a highly heterogeneous disease with variable histological appearance, biological features, clinical outcomes, and treatment responses. The number of BC cases in Saudi Arabia has more than tripled during the last 17 years to constitute 30% of all cancer cases in women. Therefore, greater efforts are needed to evaluate prognostic factors for BC in Saudi Arabia to improve prognostication and provide more personalized therapy. Recently, fragile X mental retardation syndrome-related protein 1 (FXR1) was identified as a novel biomarker that contributes to oncogenesis; however, its role in BC has not been well studied. This study aims to evaluate the clinicopathological significance of FXR1 in women with primary BC. METHODS: The protein levels of FXR1 in BC tissue samples (n=100) were determined immunohistochemically. The associations between FXR1 levels and clinicopathological parameters and outcomes were evaluated, and significant associations were validated by assessing FXR1 mRNA levels in publicly available cohorts in the BC Gene-Expression Miner database (version 5). RESULTS: High protein levels of FXR1 were significantly associated with tumor aggressiveness, including stage IIB and IIIC and hormone receptor negativity, the triple-negative BC (TNBC) subtype, and poor outcomes. Consistent with the protein results, high mRNA levels of FXR1 were significantly associated with hormone receptor negativity and the TNBC subtype. CONCLUSIONS: This study revealed that FXR1 is a prognostic factor for poor prognosis in women with BC. Further functional studies are needed to confirm its role in aggressive BC and its value as a therapeutic target.