TY - JOUR
T1 - Adaptive stress response genes associated with breast cancer subtypes and survival outcomes reveal race-related differences
AU - Al Abo, Muthana
AU - Gearhart-Serna, Larisa
AU - Van Laere, Steven
AU - Freedman, Jennifer A.
AU - Patierno, Steven R.
AU - Hwang, Eun Sil Shelley
AU - Krishnamurthy, Savitri
AU - Williams, Kevin P.
AU - Devi, Gayathri R.
N1 - Funding Information:
This work was supported in part by Duke School of Medicine Bridge Award (GRD); NCI-P20 NCCU-Duke Cancer Disparities Translational Research Partnership (S.P.; G.R.D., K.P.W., J.F.); NCI-P20 Project 2 (G.R.D., K.P.W.); NCI-P20 Predoctoral Diversity Supplement 3P20CA202925-04S2 (L.G.S.), Department of Defense Breast Cancer Breakthrough level 2 Award W81XWH-17-1-0297 (G.R.D.), NCI of NIH Award R01CA264529 (G.R.D.), The IBC Network Foundation Gift (G.R.D.), NIH Basic Research in Cancer Health Disparities R01 Award R01CA220314 (S.P., J.F.), Prostate Cancer Foundation Movember Challenge Award #18CHAL04 (S.P., J.F., M.A.). The authors would like to thank Dr. Michael Morse and Dr. Susan Dent for helpful discussions and Alexandra Bennion at Duke Undergraduate Trinity School of Arts and Science for editorial assistance.
Funding Information:
This work was supported in part by Duke School of Medicine Bridge Award (GRD); NCI-P20 NCCU-Duke Cancer Disparities Translational Research Partnership (S.P.; G.R.D., K.P.W., J.F.); NCI-P20 Project 2 (G.R.D., K.P.W.); NCI-P20 Predoctoral Diversity Supplement 3P20CA202925-04S2 (L.G.S.), Department of Defense Breast Cancer Breakthrough level 2 Award W81XWH-17-1-0297 (G.R.D.), NCI of NIH Award R01CA264529 (G.R.D.), The IBC Network Foundation Gift (G.R.D.), NIH Basic Research in Cancer Health Disparities R01 Award R01CA220314 (S.P., J.F.), Prostate Cancer Foundation Movember Challenge Award #18CHAL04 (S.P., J.F., M.A.). The authors would like to thank Dr. Michael Morse and Dr. Susan Dent for helpful discussions and Alexandra Bennion at Duke Undergraduate Trinity School of Arts and Science for editorial assistance.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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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U2 - 10.1038/s41523-022-00431-z
DO - 10.1038/s41523-022-00431-z
M3 - Article
C2 - 35697736
AN - SCOPUS:85131821640
SN - 2374-4677
VL - 8
JO - npj Breast Cancer
JF - npj Breast Cancer
IS - 1
M1 - 73
ER -