Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Nat Commun. 2021 May 10;12(1):2592. doi: 10.1038/s41467-021-22800-1.
Epithelial-to-mesenchymal transition (EMT) is the most commonly cited mechanism for cancer metastasis, but it is difficult to distinguish from profiles of normal stromal cells in the tumour microenvironment. In this study we use published single cell RNA-seq data to directly compare mesenchymal signatures from cancer and stromal cells. Informed by these comparisons, we developed a computational framework to decouple these two sources of mesenchymal expression profiles using bulk RNA-seq datasets. This deconvolution offers the opportunity to characterise EMT across hundreds of tumours and examine its association with metastasis and other clinical features. With this approach, we find three distinct patterns of EMT, associated with squamous, gynaecological and gastrointestinal cancer types. Surprisingly, in most cancer types, EMT patterns are not associated with increased chance of metastasis, suggesting that other steps in the metastatic cascade may represent the main bottleneck. This work provides a comprehensive evaluation of EMT profiles and their functional significance across hundreds of tumours while circumventing the confounding effect of stromal cells.
上皮-间充质转化（EMT）是癌症转移最常被引用的机制，但在肿瘤微环境中很难与正常基质细胞的特征区分开来。在这项研究中，我们使用已发表的单细胞 RNA-seq 数据直接比较癌症和基质细胞中的间充质特征。受这些比较的启发，我们开发了一种计算框架，使用批量 RNA-seq 数据集来分离这两个间充质表达谱来源。这种去卷积提供了在数百个肿瘤中描述 EMT 并检查其与转移和其他临床特征的关联的机会。通过这种方法，我们发现了三种不同的 EMT 模式，与鳞状细胞癌、妇科癌症和胃肠道癌症类型有关。令人惊讶的是，在大多数癌症类型中，EMT 模式与增加转移的机会无关，这表明转移级联中的其他步骤可能是主要的瓶颈。这项工作提供了对 EMT 特征及其在数百个肿瘤中的功能意义的全面评估，同时避免了基质细胞的混杂影响。
