Metatranscriptomic signatures in triple negative breast cancer

Triple-negative breast cancer (TNBC) exhibits racial disparities, with women of African ancestry (AA) experiencing higher incidence rates compared to women of European ancestry (EA). To investigate these differences, we performed a comprehensive meta-transcriptomic analysis on TNBC tumor tissues from 17 AA and 19 EA women, using microbial transcript, gene expression and microRNA expression datasets. Hierarchical clustering revealed two distinct groups primarily separated by racial ancestry, with AA tumors exhibiting higher abundance of Hafnia and elevated MIR4707 expression, while EA tumors showed increased Erwinia levels and MIR1248 expression. Cellular composition analysis using xCell demonstrated that AA tumors had higher Th1 cell abundance, whereas EA tumors contained higher M2 macrophage abundance; particularly, AA women with high M2 macrophage levels experienced poorer disease-free survival (DFS) compared to EA women. Furthermore, we identified a significant association between elevated SPDYE2B gene expression, increased Hafnia abundance, and reduced DFS, highlighting complex host-microbe interactions. These findings reveal distinct microbial and immune profiles in TNBC tumors between AA and EA patients, with specific bacterial genera and immune cell populations showing ancestry-associated patterns that may contribute to observed disparities in disease outcomes.