Clinical Significance of Annexin A2 in Predicting Poor Prognosis in African American Women with Triple-Negative Breast Cancer
Gibbs, Lee D.
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Triple-negative breast cancers (TNBC) are identified by the absence of these three major receptors that drive most breast cancer subtypes. TNBC is the most aggressive breast cancer subtype and studies have shown that the incidence of TNBC is much higher in premenopausal African American (AA) women and woman of African descent in comparison to woman of European descent. TNBC in AA women has been associated with worst overall survival after controlling for socioeconomic factors, treatment latency, and tumor receptor expression. This suggests that the clinical outcome of TNBC in AA women may result more from biological differences than access to adequate healthcare. Utilizing a large archived breast cancer cohort of genome sequencing information and the evaluation of these targets in breast tissue and serum can lead to recognition of reliable biological markers that have tremendous potential to enhance detection, treatment, and prognosis. Our previous studies have shown that Annexin A2 (AnxA2), a 36 kda calcium-dependent phospholipid binding protein, is abundantly expressed in TNBC. We have shown AnxA2 to play multiple roles in TNBC by regulating cellular functions; including plasminogen activation, angiogenesis, proliferation, migration, invasion, and metastasis. AnxA2 is one of the most identified proteins expressed in exosomes (small vesicles that are secreted from tumors as metastatic regulators). We have previously demonstrated exosomal AnxA2 contribution to metastasis of TNBC cells in vivo. The proposed study will determine the correlation of AnxA2 with poor prognoses in AA TNBC patients, and establish the clinical significance of exosomal AnxA2 in contributing to the poor clinical outcomes seen in AA TNBC patients. Three specific aims were addressed in this work. Aim 1- Determine the association of secreted exosomal AnxA2 with TNBC amongst AA patients. Aim 2 - Evaluate AnxA2 expression in TNBC tissue samples amongst a breast cancer patient cohort of various breast subtypes. Aim 3 - Determine the correlation of AnxA2 gene expression with poor pathological, prognostic variables and race/ethnicity in TNBC patients through in silico analysis.