Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry.
Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry.
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DOI：
10.1038/s41523-021-00215-x
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发表时间：
2021-02-08
影响因子：
5.9
通讯作者：
Decock J
中科院分区：
文献类型：
--
作者：
Roelands J;Mall R;Almeer H;Thomas R;Mohamed MG;Bedri S;Al-Bader SB;Junejo K;Ziv E;Sayaman RW;Kuppen PJK;Bedognetti D;Hendrickx W;Decock J
在全球癌症负担统计中，乳腺癌在很大程度上占主导地位；然而，各国之间的死亡率存在显著差异。虽然社会经济因素造成了基于人口的死亡率差异，但它们不能完全解释非洲血统(AA)和阿拉伯血统(ARA)妇女与欧洲血统妇女(EA)之间的差异。在这项研究中，我们试图确定分子差异，这些差异可以为临床结果中祖先相关差异的生物学提供洞察力。我们应用了一种独特的方法，结合使用来自癌症基因组图谱(TCGA)泛癌症临床数据源的精选生存数据，改进的基于单核苷酸多态的推断祖先分配，以及一种新的乳腺癌亚型分类来询问TCGA和当地的阿拉伯乳腺癌数据集。我们观察到AA患者的BasalMyo肿瘤丰富(EA组38vs16.5%，p = 1.30E − 10)，总体上显著恶化(危险比(HR) = 2.39，p = 0.02)和疾病特异性生存期(HR = 2.57，p = 0.03)。BasalMyo AA和EA样本的基因集浓缩分析显示，T调节细胞和T辅助2型细胞的丰度不同，与癌症相关的具有预后意义的通路(AA：PI3K-Akt-mTOR和ErbB信号；EA：EGF、雌激素依赖和DNA修复信号)不同。值得注意的是，AMPK信号与相反的预后内涵相关(AA：10年HR = 为2.79，EA：10年HR = 为0.34)。对ARA患者的分析表明，BasalMyo肿瘤丰富，有T调节细胞和AMPK信号的差异性丰富的趋势。综上所述，我们的发现表明，AA乳腺癌患者临床结果的差异可能与癌症相关特征和微环境特征的差异有关。
Breast cancer largely dominates the global cancer burden statistics; however, there are striking disparities in mortality rates across countries. While socioeconomic factors contribute to population-based differences in mortality, they do not fully explain disparity among women of African ancestry (AA) and Arab ancestry (ArA) compared to women of European ancestry (EA). In this study, we sought to identify molecular differences that could provide insight into the biology of ancestry-associated disparities in clinical outcomes. We applied a unique approach that combines the use of curated survival data from The Cancer Genome Atlas (TCGA) Pan-Cancer clinical data resource, improved single-nucleotide polymorphism-based inferred ancestry assignment, and a novel breast cancer subtype classification to interrogate the TCGA and a local Arab breast cancer dataset. We observed an enrichment of BasalMyo tumors in AA patients (38 vs 16.5% in EA, p = 1.30E − 10), associated with a significant worse overall (hazard ratio (HR) = 2.39, p = 0.02) and disease-specific survival (HR = 2.57, p = 0.03). Gene set enrichment analysis of BasalMyo AA and EA samples revealed differences in the abundance of T-regulatory and T-helper type 2 cells, and enrichment of cancer-related pathways with prognostic implications (AA: PI3K-Akt-mTOR and ErbB signaling; EA: EGF, estrogen-dependent and DNA repair signaling). Strikingly, AMPK signaling was associated with opposing prognostic connotation (AA: 10-year HR = 2.79, EA: 10-year HR = 0.34). Analysis of ArA patients suggests enrichment of BasalMyo tumors with a trend for differential enrichment of T-regulatory cells and AMPK signaling. Together, our findings suggest that the disparity in the clinical outcome of AA breast cancer patients is likely related to differences in cancer-related and microenvironmental features.
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影响因子：
50.3
作者：
Carrot-Zhang, Jian;Chambwe, Nyasha;Beroukhim, Rameen
通讯作者：
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