10x Genomics Inc., Pleasanton, CA, 94566, USA.
Nat Commun. 2023 Dec 19;14(1):8353. doi: 10.1038/s41467-023-43458-x.
Single-cell and spatial technologies that profile gene expression across a whole tissue are revolutionizing the resolution of molecular states in clinical samples. Current commercially available technologies provide whole transcriptome single-cell, whole transcriptome spatial, or targeted in situ gene expression analysis. Here, we combine these technologies to explore tissue heterogeneity in large, FFPE human breast cancer sections. This integrative approach allowed us to explore molecular differences that exist between distinct tumor regions and to identify biomarkers involved in the progression towards invasive carcinoma. Further, we study cell neighborhoods and identify rare boundary cells that sit at the critical myoepithelial border confining the spread of malignant cells. Here, we demonstrate that each technology alone provides information about molecular signatures relevant to understanding cancer heterogeneity; however, it is the integration of these technologies that leads to deeper insights, ushering in discoveries that will progress oncology research and the development of diagnostics and therapeutics.
单细胞和空间技术可以在整个组织中对基因表达进行分析，从而彻底改变临床样本中分子状态的解析。目前市场上有提供全转录组单细胞、全转录组空间或靶向原位基因表达分析的技术。在这里，我们结合这些技术来探索大型 FFPE 人乳腺癌切片中的组织异质性。这种综合方法使我们能够探索不同肿瘤区域之间存在的分子差异，并鉴定参与向浸润性癌进展的生物标志物。此外，我们研究了细胞邻域并鉴定了罕见的边界细胞，这些细胞位于限制恶性细胞扩散的关键肌上皮边界处。在这里，我们证明每种技术本身都提供了与理解癌症异质性相关的分子特征信息；然而，正是这些技术的整合带来了更深入的见解，为肿瘤学研究以及诊断和治疗方法的发展带来了新的发现。
