Adaptive stress response genes associated with breast cancer subtypes and survival outcomes reveal race-related differences

Abstract

Abstract Aggressive breast cancer variants, like triple negative and inflammatory breast cancer, contribute to disparities in survival and clinical outcomes among African American (AA) patients compared to White (W) patients. We previously identified the dominant role of anti-apoptotic protein XIAP in regulating tumor cell adaptive stress response (ASR) that promotes a hyperproliferative, drug resistant phenotype. Using The Cancer Genome Atlas (TCGA), we identified 46–88 ASR genes that are differentially expressed (2-fold-change and adjusted p-value < 0.05) depending on PAM50 breast cancer subtype. On average, 20% of all 226 ASR genes exhibited race-related differential expression. These genes were functionally relevant in cell cycle, DNA damage response, signal transduction, and regulation of cell death-related processes. Moreover, 23% of the differentially expressed ASR genes were associated with AA and/or W breast cancer patient survival. These identified genes represent potential therapeutic targets to improve breast cancer outcomes and mitigate associated health disparities.