Abstract C036: Correlation of Kaiso and androgen receptor expression in women of African ancestry with triple-negative breast cancer
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AbstractBreast cancer (BCa) is the most frequently diagnosed female cancer and a leading cause of female deaths worldwide, regardless of increased awareness and improved therapies. Triple-negative breast cancer (TNBC) is one of the most challenging BCa subtypes as it is highly heterogeneous, metastatic in nature and has limited targeted therapies. TNBC is most prevalent in young women of African ancestry (WAA), who despite having lower BCa rates, have a disproportionately higher mortality rate compared to women of European ancestry (WEA). However, the cause for this racial disparity is currently unknown, thus highlighting the importance of unraveling the genetic and molecular factors that contribute to TNBC in WAA. Our lab previously showed that the transcription factor Kaiso may be linked to this disparity as it contributes to increased metastasis and mortality in WAA TNBC patients. Interestingly, multiple studies have indicated that WAA TNBC tissues also express less Androgen Receptor (AR) than WEA TNBC tissues, supporting the existence of a novel BCa subtype – quadruple-negative breast cancer (QNBC). Notably, in silico analysis revealed several Kaiso binding sites in the AR promoter region, and that high Kaiso and low AR expression correlated with poorer overall survival in BCa patients. Thus, we hypothesized that high Kaiso and low AR expression could be contributing to the increased mortality in WAA with TNBC. This study seeks to examine the relationship between Kaiso and AR, the clinical significance of this relationship and its role, if any, in TNBC racial disparities. Using tissue microarrays (TMAs) and immunohistochemistry (IHC), we found reduced and cytoplasmic AR expression in WAA compared to WEA. Moreover, preliminary findings from western blot analyses showed an increase in AR expression in response to Kaiso depletion in TNBC cells. These findings suggest that AR could be a bona fide Kaiso target gene and that there may be clinical relevance of high Kaiso, and low AR expression in BCa survival, especially in patients with an African heritage. Ongoing experiments are focused on determining if Kaiso directly associates with the endogenous AR promoter region and discerning the link between high Kaiso and low AR expression in TNBC racial disparities. A significant correlation between Kaiso and AR expression will help to validate the existence of QNBC in WAA and support Kaiso and AR as clinically relevant prognostic markers for TNBC, especially in WAA.Citation Format: Stephanie Ali Fairbairn, Robert Cowan, Juliet M. Daniel, Shawn M. Hercules. Correlation of Kaiso and androgen receptor expression in women of African ancestry with triple-negative breast cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C036.
