PO.MCB08.03 · 分子与细胞生物学
三阴性乳腺癌中的宏转录组学特征
Metatranscriptomic signatures in triple negative breast cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
三阴性乳腺癌(TNBC)存在种族差异,非洲裔(AA)女性的发病率高于欧洲裔(EA)女性。为探究这些差异,我们对来自17名AA女性和19名EA女性的TNBC肿瘤组织进行了全面的宏转录组学分析,使用了微生物转录本、基因表达和microRNA表达数据集。层次聚类揭示出两个主要按种族血统分开的不同群组,其中AA肿瘤表现出更高丰度的Hafnia和升高的MIR4707表达,而EA肿瘤则显示出Erwinia水平升高和MIR1248表达升高。使用xCell进行的细胞组成分析表明,AA肿瘤中Th1细胞丰度更高,而EA肿瘤中M2巨噬细胞丰度更高;特别是,M2巨噬细胞水平高的AA女性相比EA女性经历了更差的无病生存期(DFS)。此外,我们发现SPDYE2B基因表达升高、Hafnia丰度增加与DFS缩短之间存在显著关联,凸显了复杂的宿主-微生物相互作用。这些发现揭示了AA与EA患者TNBC肿瘤之间不同的微生物和免疫特征,特定的细菌属和免疫细胞群显示出与血统相关的模式,可能是造成所观察到的疾病结局差异的原因。
查看英文原文 English abstract
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.
利益披露 Disclosure
R. Kumar, None..
G. Shahrokhi, None..
S. Shaikh, None..
S. Negedu, None..
N. He, None.