Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Bruker-MUSC Center of Excellence, Clinical Glycomics, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425, United States.
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 96 Jonathan Lucas St. Ste. 601, MSC 617, Charleston, SC 29425, United States.
Glycobiology. 2024 Jun 22;34(8). doi: 10.1093/glycob/cwae043.
Higher breast cancer mortality rates continue to disproportionally affect black women (BW) compared to white women (WW). This disparity is largely due to differences in tumor aggressiveness that can be related to distinct ancestry-associated breast tumor microenvironments (TMEs). Yet, characterization of the normal microenvironment (NME) in breast tissue and how they associate with breast cancer risk factors remains unknown. N-glycans, a glucose metabolism-linked post-translational modification, has not been characterized in normal breast tissue. We hypothesized that normal female breast tissue with distinct Breast Imaging and Reporting Data Systems (BI-RADS) categories have unique microenvironments based on N-glycan signatures that varies with genetic ancestries. Profiles of N-glycans were characterized in normal breast tissue from BW (n = 20) and WW (n = 20) at risk for breast cancer using matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). A total of 176 N-glycans (32 core-fucosylated and 144 noncore-fucosylated) were identified in the NME. We found that certain core-fucosylated, outer-arm fucosylated and high-mannose N-glycan structures had specific intensity patterns and histological distributions in the breast NME dependent on BI-RADS densities and ancestry. Normal breast tissue from BW, and not WW, with heterogeneously dense breast densities followed high-mannose patterns as seen in invasive ductal and lobular carcinomas. Lastly, lifestyles factors (e.g. age, menopausal status, Gail score, BMI, BI-RADS) differentially associated with fucosylated and high-mannose N-glycans based on ancestry. This study aims to decipher the molecular signatures in the breast NME from distinct ancestries towards improving the overall disparities in breast cancer burden.
黑人女性（BW）的乳腺癌死亡率持续居高不下，与白人女性（WW）相比极不均衡。这种差异主要归因于肿瘤侵袭性的不同，这可能与独特的与祖先相关的乳腺癌肿瘤微环境（TME）有关。然而，正常乳腺组织的微环境（NME）特征以及它们如何与乳腺癌的危险因素相关仍不清楚。N-糖基化，一种与葡萄糖代谢相关的翻译后修饰，尚未在正常乳腺组织中得到描述。我们假设，根据 N-糖基化特征，具有不同乳腺成像和报告数据系统（BI-RADS）分类的正常女性乳腺组织具有独特的微环境，这些特征因遗传起源而异。使用基质辅助激光解吸/电离（MALDI）质谱成像（MSI），我们对 BW（n=20）和 WW（n=20）中具有乳腺癌风险的正常乳腺组织中的 N-糖进行了特征分析。在 NME 中鉴定出 176 种 N-聚糖（32 种核心岩藻糖基化和 144 种非核心岩藻糖基化）。我们发现，某些核心岩藻糖基化、外臂岩藻糖基化和高甘露糖 N-聚糖结构在乳腺 NME 中具有特定的强度模式和组织学分布，这取决于 BI-RADS 密度和起源。BW 的正常乳腺组织，而不是 WW，具有不均匀致密的乳腺密度，表现出与浸润性导管癌和小叶癌相同的高甘露糖模式。最后，生活方式因素（如年龄、绝经状态、 Gail 评分、BMI、BI-RADS）根据起源与岩藻糖基化和高甘露糖 N-聚糖存在差异关联。本研究旨在解析来自不同起源的乳腺 NME 的分子特征，以改善乳腺癌负担的整体差异。
