Abstract Despite significant progress in elucidating the biology of breast cancer, there remains a need for biomarkers for accurate prognostic stratification and prediction of therapeutic response. In the present study, we sought to determine the protein expression pattern and prognostic value of RUVBL1 alone or in combination with SPARC in breast cancer. We performed IHC analysis using antibodies against RUVBL1 and SPARC on a tissue microarray comprising 319 primary breast tumor samples. RUVBL1, a member of the highly conserved ATPases of the AAA+ superfamily, is involved in key cellular processes related to tumorigenesis. Our previous work has shown that the downregulation of SPARC protein expression, a matricellular protein with pleiotropic functions, is an independent prognostic factor for breast cancer. RUVBL1 expression was positively associated with HER2 positivity (p=0.006), post-menopausal status (p=0.007), and reduced ER/PR expression (p=0.046). Although we did not observe any significant prognostic value of RUVBL1 expression in our population, we observed a strong association between RUVBL1 and SPARC expression (p0.0001). Moreover, the combined profile of high RUVBL1 and low SPARC expression stratified a subgroup of patients with markedly poorer survival outcomes (HR=2.49, 95% CI: 1.36–4.56, p=0.003), exhibiting a survival rate of 17%. Our results provide novel insights supporting the prognostic significance of RUVBL1 and SPARC in breast cancer. These findings underscore the need for further experimental and clinical investigations to fully understand the clinical implications of RUVBL1 and SPARC expression in breast cancer. Citation Format: Flavia Rotea Mangone, Fernando A. Soares, Maria Aparecida Nagai. RUVBL1 and SPARC as prognostic biomarkers in breast cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7917.
Mangone et al. (Fri,) studied this question.