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.
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.
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.
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.
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Breast cancer stem cells
Fluorescent activated cell sorting
Gene Ontology Consortium
Hematoxylin and eosin
Komfo Anokye Teaching Hospital
Kyoto Encyclopedia of Genes and Genomes
Principal component analysis
Triple-negative breast cancer
The University of Michigan
Western sub-Saharan Africans
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Work supported in part by the Komen for the Cure Promise grant (LN, MW, JC), the Breast Cancer Research Foundation (MW, SDM), the Metavivor Foundation (SDM), the Rackham Barbour Scholarship, UM Cancer Center Support Grant P30 CA 046592, and the ULAM In Vivo Animal Core histopathology laboratory.
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Jiagge, E.M., Ulintz, P.J., Wong, S. et al. Multiethnic PDX models predict a possible immune signature associated with TNBC of African ancestry. Breast Cancer Res Treat 186, 391–401 (2021). https://doi.org/10.1007/s10549-021-06097-8
- Triple-negative breast cancer
- Breast cancer stem cells
- African ancestry
- Gene expression