Racial Variation in Annexin A2 (AnxA2) Gene Expression and Poor Outcome in Triple-Negative Breast Cancer

Background: Triple-negative breast cancer (TNBC) is identified by the absence of three major receptors that drive most breast cancers and is a health disparity issue due to its disproportionate occurrence in African American (AA) women. Previous studies have identified elevated levels of AnxA2 in TNBC cell lines, but its association with racial variation and outcomes is unknown. Methods: AnxA2 gene expression was evaluated in TNBC and non-TNBC cases from The Cancer Genome Atlas (TCGA) RNAseqV2 database. Associations between clinical outcomes and AnxA2 gene expression were tested in a genome wide association study of combined publically available datasets. Results: AnxA2 gene expression was elevated in TNBC in comparison to other breast cancer subtypes. Furthermore, AnxA2 gene expression is elevated in AA women and is associated with the disproportionate occurrence of TNBC. High expression levels of AnxA2 is associated with reduced overall survival (hazard =2.66; 95% confidence interval {CI] = 1.14 - 6.25, P = 0.0192), reduced relapse free survival (hazard = 1.45; 95% confidence interval {CI] = 1.12 – 1.89, P = 0.0051), and reduced distant metastasis free survival (hazard = 1.7; 95% confidence interval {CI] = 1.00 – 2.91, P = 0.048). AnxA2 gene expression was not associated with poor outcome in other subtypes, indicating the specificity of AnxA2 contribution to the aggressive behavior of TNBC. Conclusion: AnxA2 overexpression is associated with racial variation and is a potential prognostic candidate for TNBC. AnxA2 has potential prognostic value, implicating a role for AnxA2 in the aggressive biology of TNBC in AA women.