文章：

回顾性审视三阴性乳腺癌微环境：基于公共单细胞RNA测序数据集的新型标志物、相互作用及肿瘤相关组分机制研究

A Retrospective View of the Triple-Negative Breast Cancer Microenvironment: Novel Markers, Interactions, and Mechanisms of Tumor-Associated Components Using Public Single-Cell RNA-Seq Datasets

原文发布日期：16 March 2024

DOI: 10.3390/cancers16061173

类型: Article

开放获取: 是

英文摘要：

Triple-negative breast cancer (TNBC) is a significant clinical challenge due to its aggressive nature and limited treatment options. In search of new treatment targets, not only single genes but also gene pairs involved in protein interactions, we explored the tumor microenvironment (TME) of TNBC from a retrospective point of view, using public single-cell RNA sequencing datasets. A High-resolution Cell type Annotation Tool, HiCAT, was used first to identify the cell type in 3-level taxonomies. Tumor cells were then identified based on the estimates of copy number variation. With the annotation results, differentially expressed genes were analyzed to find subtype-specific markers for each cell type, including tumor cells, fibroblast, and macrophage. Cell–cell interactions were also inferred for each cell type pair. Through integrative analysis, we could find unique TNBC markers not only for tumor cells but also for various TME components, including fibroblasts and macrophages. Specifically, twelve marker genes, includingDSC2andCDKN2A, were identified for TNBC tumor cells. Another key finding of our study was the interaction between theDSC2andDSG2genes among TNBC tumor cells, suggesting that they are more tightly aggregated with each other than those of other subtypes, including normal epithelial cells. The overexpression ofDSC2in TNBC and its prognostic power were verified by using METABRIC, a large bulk RNA-seq dataset with clinical information. These findings not only corroborate previous hypotheses but also lay the foundation for a new structural understanding of TNBC, as revealed through our single-cell analysis workflow.

摘要翻译： 

三阴性乳腺癌（TNBC）因其侵袭性强和治疗选择有限而构成重大临床挑战。为寻找新的治疗靶点，不仅关注单个基因，还关注参与蛋白质相互作用的基因对，我们利用公共单细胞RNA测序数据集，从回顾性角度探索了TNBC的肿瘤微环境（TME）。首先使用高分辨率细胞类型注释工具HiCAT进行三级分类的细胞类型鉴定。随后基于拷贝数变异估计识别肿瘤细胞。利用注释结果，通过差异表达基因分析，为包括肿瘤细胞、成纤维细胞和巨噬细胞在内的每种细胞类型寻找亚型特异性标志物。同时推断了每种细胞类型对之间的细胞间相互作用。通过整合分析，我们不仅发现了TNBC肿瘤细胞的独特标志物，还鉴定了包括成纤维细胞和巨噬细胞在内的多种TME成分的特异性标志物。其中，针对TNBC肿瘤细胞鉴定出包括DSC2和CDKN2A在内的12个标志基因。本研究的另一关键发现是TNBC肿瘤细胞中DSC2与DSG2基因间的相互作用，表明其细胞间聚集程度较其他亚型（包括正常上皮细胞）更为紧密。通过使用具有临床信息的大样本RNA测序数据集METABRIC，验证了DSC2在TNBC中的过表达及其预后预测能力。这些发现不仅证实了先前的假设，更为通过单细胞分析流程揭示的TNBC新结构理解奠定了基础。

原文链接：

A Retrospective View of the Triple-Negative Breast Cancer Microenvironment: Novel Markers, Interactions, and Mechanisms of Tumor-Associated Components Using Public Single-Cell RNA-Seq Datasets