TROP2 and immune gene expression by African ancestry in triple-negative breast cancer
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Purpose
TROP2 is a treatment target in triple-negative breast cancer (TNBC). TACSTD2 encodes TROP2, while PDCD1 encodes the immune protein PD-1. We investigated whether these genes differ by race or African genetic ancestry and whether the reported link between higher TACSTD2 and lower immune-gene expression partly reflects the mixture of cells in tumor samples.
Methods
We analyzed TNBC tumors from TCGA (n = 107) and GSE268851 (n = 253; ancestry data for 229), together with spatial, normal-breast, and protein datasets. Regression models adjusted for age, tumor stage, and a score based on epithelial gene expression. We compared TACSTD2 with other epithelial markers using paired bootstrap analysis.
Results
TACSTD2 was detected in nearly all tumors, with no significant differences by race or ancestry. Higher African ancestry was linked to higher PDCD1 expression in TCGA (P = 3.9 × 10 −4 ), but not in GSE268851. In GSE268851, higher TACSTD2 remained associated with lower CD8A, GZMB , and cytotoxic score after epithelial adjustment (all q < 0.003). These associations were stronger than those for EPCAM ; the CD8A association was also stronger than that for KRT8. TACSTD2 was 1.55-fold higher in TNBC than in normal breast and correlated with TROP2 protein (ρ = 0.74).
Conclusion
TACSTD2 was widely expressed in the TNBC groups studied, while the ancestry– PDCD1 association differed between cohorts. Epithelial gene expression did not fully explain some negative TACSTD2 –immune associations, and some were stronger than those for other epithelial markers such as EPCAM .
Article activity feed
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TROP2 and immune gene expression by African ancestry in triple-negative breast cancer https://www.biorxiv.org/content/10.64898/2026.10.29.762976v1
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TROP2 and immune gene expression by African ancestry in triple-negative breast cancer https://www.biorxiv.org/content/10.64898/2026.10.29.762976v1
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