肿瘤内部微生物群落和基因组特征的共同分析揭示了不同种族之间在乳腺癌方面的明显差异。
Concomitant analyses of intratumoral microbiota and genomic features reveal distinct racial differences in breast cancer.
发表日期:2023 Jan 26
作者:
Sheetal Parida, Sumit Siddharth, Yuqing Xia, Dipali Sharma
来源:
npj Breast Cancer
摘要:
种族不平等在黑人女性中表现最为明显,因为她们患乳腺癌的终身风险低于白人和亚洲女性,但她们的乳腺癌相关死亡率是所有种族中最高的。黑人女性更有可能在更年轻时发展三阴性乳腺癌并携带更具侵袭性的肿瘤。除了肿瘤中心的改变外,肿瘤生长还受到其他多个与肿瘤微环境相关的特征影响,包括细胞免疫和微生物群落。因此,在本研究中,我们进行了同时进行基因组和微生物组分析,并揭示了亚洲、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和肿瘤免疫微环境相关特征。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节点。细胞异质性的检查显示,不同种族群体的乳腺肿瘤中有11种免疫和基质细胞类型的富集程度不同。在微生物多样性方面,α和β多样性测量中均有显著差异。有趣的是,鉴定出了潜在的与种族相关的乳腺癌微生物标志物,这些标志物显著与涉及肿瘤侵袭性、血管生成、肿瘤细胞迁移和转移以及致癌途径GLI和Notch等基因相关联。调查肿瘤内微生物代谢特征时,我们发现环境信息处理途径、致癌途径和脂质代谢途径的富集程度显著不同。同时研究肿瘤中心、肿瘤免疫微环境相关和微生物变化,本研究提供了对乳腺癌种族不平等的全面理解,并需要进一步探索。(翻译者注:原文中某些专有名词可能需要根据具体情况翻译)©2023.作者。
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.© 2023. The Author(s).