Table_3_Diversity and heterogeneity in human breast cancer adipose tissue revealed at single-nucleus resolution.xls

IntroductionThere is increasing awareness of the role of adipose tissue in breast cancer occurrence and development, but no comparison of adipose adjacent to breast cancer tissues and adipose adjacent to normal breast tissues has been reported.
MethodsSingle-nucleus RNA sequencing (snRNA-seq) was used to analyze cancer-adjacent and normal adipose tissues from the same breast cancer patient to characterize heterogeneity. SnRNA-seq was performed on 54513 cells from six samples of normal breast adipose tissue (N) distant from the tumor and tumor-adjacent adipose tissue (T) from the three patients (all surgically resected).
Results and discussionSignificant diversity was detected in cell subgroups, differentiation status and, gene expression profiles. Breast cancer induces inflammatory gene profiles in most adipose cell types, such as macrophages, endothelial cells, and adipocytes. Furthermore, breast cancer decreased lipid uptake and the lipolytic phenotype and caused a switch to lipid biosynthesis and an inflammatory state in adipocytes. The in vivo trajectory of adipogenesis revealed distinct transcriptional stages. Breast cancer induced reprogramming across many cell types in breast cancer adipose tissues. Cellular remodeling was investigated by alterations in cell proportions, transcriptional profiles and cell-cell interactions. Breast cancer biology and novel biomarkers and therapy targets may be exposed.

引言：当前学界对脂肪组织在乳腺癌发生与发展过程中的作用认知不断深化，但目前尚无针对乳腺癌组织毗邻脂肪与正常乳腺毗邻脂肪组织的对比研究报道。
方法：本研究采用单细胞核RNA测序（single-nucleus RNA sequencing，snRNA-seq），对同一乳腺癌患者的癌旁脂肪组织与正常乳腺脂肪组织进行分析，以解析其异质性。研究共纳入3例经手术切除的乳腺癌患者样本，每份患者样本分别获取远离肿瘤的正常乳腺脂肪组织（N组）与肿瘤邻近脂肪组织（T组）各1份，总计6份样本，对其中的54513个细胞完成了snRNA-seq检测。
结果与讨论：本研究在细胞亚群、分化状态及基因表达谱中均检测到显著差异。乳腺癌可使巨噬细胞、内皮细胞、脂肪细胞等多数脂肪细胞类型呈现炎症相关基因表达谱特征。进一步研究发现，乳腺癌可降低脂肪细胞的脂质摄取能力与脂解表型，并促使其转向脂质生物合成与炎症状态。体内脂肪生成轨迹显示出清晰可辨的转录阶段。乳腺癌可诱导乳腺癌旁脂肪组织内多种细胞类型发生重编程。研究通过分析细胞比例变化、转录谱特征及细胞间互作情况，对细胞重塑过程进行了探究。本研究或可揭示乳腺癌的生物学特性、新型生物标志物及治疗靶点。