Parida Sheetal, Siddharth Sumit, Xia Yuqing, Sharma Dipali
Department of Oncology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
NPJ Breast Cancer. 2023 Jan 26;9(1):4. doi: 10.1038/s41523-023-00505-6.
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.
种族差异在黑人女性中最为突出，因为她们患乳腺癌的终生风险低于白人和亚洲女性，但她们与乳腺癌相关的死亡率在所有种族中却是最高的。黑人女性更有可能在年轻时患上三阴性乳腺癌，且携带更具侵袭性的肿瘤。除了以肿瘤为中心的改变外，肿瘤生长还受到多种其他与肿瘤微环境相关的特征影响，包括驻留免疫细胞和微生物群。因此，在本研究中，我们同时进行了基因组和宏基因组分析，揭示了亚洲、黑人和白人女性乳腺肿瘤中独特的肿瘤内微生物群落组成以及与肿瘤免疫微环境相关的特征。有趣的是，在亚洲、黑人和白人女性的乳腺肿瘤中发现了独特的种族相关基因组节点。对细胞异质性的检查显示，不同种族组乳腺肿瘤中64种免疫和基质细胞类型中的11种存在差异富集。在微生物多样性方面，α和β多样性测量显示出显著差异。有趣的是，还鉴定出了乳腺癌潜在的种族特异性微生物生物标志物，它们与参与肿瘤侵袭性、血管生成、肿瘤细胞迁移和转移以及致癌途径-GLI和Notch的基因显著相关。通过研究肿瘤内微生物的代谢特征，我们发现环境信息处理途径、致癌途径和脂质代谢途径存在显著的差异富集。同时研究以肿瘤为中心、与肿瘤免疫微环境相关的以及微生物的改变，我们的研究全面了解了乳腺癌中的种族差异，值得进一步探索。
