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

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.

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Published Version (Please cite this version)

10.1038/s41523-022-00431-z

Publication Info

Al Abo, Muthana, Larisa Gearhart-Serna, Steven Van Laere, Jennifer A Freedman, Steven R Patierno, Eun-Sil Shelley Hwang, Savitri Krishnamurthy, Kevin P Williams, et al. (2022). Adaptive stress response genes associated with breast cancer subtypes and survival outcomes reveal race-related differences. NPJ breast cancer, 8(1). p. 73. 10.1038/s41523-022-00431-z Retrieved from https://hdl.handle.net/10161/26060.

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Scholars@Duke

Freedman

Jennifer Freedman

Associate Professor in Medicine
Patierno

Steven Patierno

Charles D. Watts Distinguished Professor of Medicine

Patierno's current translational research interests are focused on the genomics molecular biology of cancer disparities, cancer biology, molecular pharmacology and targeted experimental therapeutics to control prostate, breast and lung tumor aggressiveness. He is an internationally recognized expert in cancer control, cancer causation and molecular carcinogenesis, which includes a broad spectrum of laboratory and population level research.   Patierno is also actively engaged in cancer health disparities and healthcare delivery research focused on patient navigation, survivorship, community-based interventions, mHealth, implementation sciences, cancer care economics, and policy.

Devi

Gayathri R. Devi

Professor in Surgery

Dr. Devi’s research interests include functional genomics, anti-cancer drug discovery and development, mechanisms of cancer cell signaling, tumor immunity and applications thereof for overcoming therapeutic resistance in cancer.

The lab has established prostate, inflammatory breast cancer and ovarian cellular and tumor models.


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