Concomitant analyses of intratumoral microbiota and genomic features reveal distinct racial differences in breast cancer

Abstract

Racial disparities are most accentuated among Black women as their lifetime risk of breast cancer incidence is lower than white and Asian women but their breast cancer related mortality is the highest among all races. Black women are more likely to develop triple-negative breast cancer at a younger age and harbor more aggressive tumors. In addition to tumor-centric alterations, tumor growth is also influenced by multiple other tumor microenvironment-related features, including resident immune cells and microbiota. Hence, in this study, we conduct concurrent genomic and metagenomic analyses, and uncover distinctive intratumoral microbial community compositions and tumor immune microenvironment-related traits in breast tumors from Asian, Black and white women. Interestingly, unique racially associated genomic nodes are found in the breast tumors from Asian, Black and white women. Examination of the cellular heterogeneity show differential enrichment of 11 out of 64 immune and stroma cell types in the breast tumors from different racial groups. In terms of microbial diversity, significant differences are revealed in alpha and beta-diversity measures. Intriguingly, potential race-specific microbial biomarkers of breast cancer are identified which significantly correlate with genes involved with tumor aggressiveness, angiogenesis, tumor cell migration and metastasis as well as oncogenic pathways-GLI and Notch. Investigating the metabolic features of intratumoral microbes, we find a significant differential enrichment of environmental information processing pathways, oncogenic pathways, and lipid metabolism pathways. Concomitantly investigating tumor-centric, tumor immune microenvironment-related and microbial alterations, our study provides a comprehensive understanding of racial disparities in breast cancer and warrants further exploration.