Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.
Nat Commun. 2024 Mar 18;15(1):2009. doi: 10.1038/s41467-024-46320-w.
The molecular characteristics of metastatic upper tract urothelial carcinoma (UTUC) are not well understood, and there is a lack of knowledge regarding the genomic and transcriptomic differences between primary and metastatic UTUC. To address these gaps, we integrate whole-exome sequencing, RNA sequencing, and Imaging Mass Cytometry using lanthanide metal-conjugated antibodies of 44 tumor samples from 28 patients with high-grade primary and metastatic UTUC. We perform a spatially-resolved single-cell analysis of cancer, immune, and stromal cells to understand the evolution of primary to metastatic UTUC. We discover that actionable genomic alterations are frequently discordant between primary and metastatic UTUC tumors in the same patient. In contrast, molecular subtype membership and immune depletion signature are stable across primary and matched metastatic UTUC. Molecular and immune subtypes are consistent between bulk RNA-sequencing and mass cytometry of protein markers from 340,798 single cells. Molecular subtypes at the single-cell level are highly conserved between primary and metastatic UTUC tumors within the same patient.
转移性上尿路尿路上皮癌（UTUC）的分子特征尚不清楚，对于原发性和转移性 UTUC 之间的基因组和转录组差异知之甚少。为了解决这些空白，我们整合了全外显子测序、RNA 测序和使用镧系金属偶联抗体的成像质谱细胞检测，对 28 名高级别原发性和转移性 UTUC 患者的 44 个肿瘤样本进行了分析。我们对癌症、免疫和基质细胞进行了空间分辨的单细胞分析，以了解原发性向转移性 UTUC 的演变。我们发现，同一患者的原发性和转移性 UTUC 肿瘤之间，可采取行动的基因组改变经常不一致。相比之下，分子亚型成员和免疫耗竭特征在原发性和匹配的转移性 UTUC 之间是稳定的。来自 340798 个单细胞的批量 RNA 测序和蛋白标志物的质谱细胞检测结果表明，分子和免疫亚型是一致的。在同一患者中，原发性和转移性 UTUC 肿瘤之间的单细胞水平的分子亚型高度保守。
