Multiethnic PDX models predict a possible immune signature associated with TNBC of African ancestry

Purpose Triple-negative breast cancer (TNBC) is an aggressive subtype most prevalent among women of Western Sub-Saharan African ancestry. It accounts for 15–25% of African American (AA) breast cancers (BC) and up to 80% of Ghanaian breast cancers, thus contributing to outcome disparities in BC for b...

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Published in:	Breast cancer research and treatment 2021-04, Vol.186 (2), p.391-401
Main Authors:	Jiagge, Evelyn M., Ulintz, Peter J., Wong, Shukmei, McDermott, Sean P., Fossi, Sabrina I., Suhan, Tahra K., Hoenerhoff, Mark J., Bensenhaver, Jessica M., Salem, Barbara, Dziubinski, Michele, Oppong, Joseph K., Aitpillah, Francis, Ishmael, Kyei, Osei-Bonsu, Ernest, Adjei, Ernest, Baffour, Awuah, Aldrich, Jessica, Kurdoglu, Ahmet, Fernando, Kurt, Craig, David W., Trent, Jeff M., Li, Jun, Chitale, Dhananjay, Newman, Lisa A., Carpten, John D., Wicha, Max S., Merajver, Sofia D.
Format:	Article
Language:	eng
Subjects:	African Americans African Americans - genetics Analysis Breast cancer Female Gene expression Genes Ghana - epidemiology Growth hormone Humans Medicine Medicine & Public Health Metastases Metastasis Neoplasm Recurrence, Local Oncology PD-L1 protein Preclinical Study Stem cells Therapeutic targets Triple Negative Breast Neoplasms - genetics Tumors Whites Xenografts
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Summary:	Purpose Triple-negative breast cancer (TNBC) is an aggressive subtype most prevalent among women of Western Sub-Saharan African ancestry. It accounts for 15–25% of African American (AA) breast cancers (BC) and up to 80% of Ghanaian breast cancers, thus contributing to outcome disparities in BC for black women. The aggressive biology of TNBC has been shown to be regulated partially by breast cancer stem cells (BCSC) which mediate tumor recurrence and metastasis and are more abundant in African breast tumors. Methods We studied the biological differences between TNBC in women with African ancestry and those of Caucasian women by comparing the gene expression of the BCSC. From low-passage patient derived xenografts (PDX) from Ghanaian (GH), AA, and Caucasian American (CA) TNBCs, we sorted for and sequenced the stem cell populations and analyzed for differential gene enrichment. Results In our cohort of TNBC tumors, we observed that the ALDH expressing stem cells display distinct ethnic specific gene expression patterns, with the largest difference existing between the GH and AA ALDH+ cells. Furthermore, the tumors from the women of African ancestry [GH/AA] had ALDH stem cell (SC) enrichment for expression of immune related genes and processes. Among the significantly upregulated genes were CD274 (PD-L1), CXCR9, CXCR10 and IFI27, which could serve as potential drug targets. Conclusions Further exploration of the role of immune regulated genes and biological processes in BCSC may offer insight into developing novel approaches to treating TNBC to help ameliorate survival disparities in women with African ancestry.
ISSN:	0167-6806 1573-7217