The evolution of metastatic upper tract urothelial carcinoma through genomic-transcriptomic and single-cell protein markers analysis.
The evolution of metastatic upper tract urothelial carcinoma through genomic-transcriptomic and single-cell protein markers analysis.
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通过基因组转录组和单细胞蛋白标记物分析转移性上尿路上皮癌的演变。
DOI：
10.1038/s41467-024-46320-w
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发表时间：
2024
影响因子：
16.6
通讯作者：
Kha
中科院分区：
文献类型：
--
作者：
Ohara,Kentaro;Rendeiro,AndréFigueiredo;Bhinder,Bhavneet;Eng,KennethWha;Ravichandran,Hiranmayi;Nguyen,Duy;Pisapia,David;Vosoughi,Aram;Fernandez,Evan;Shohdy,KyrillusS;Manohar,Jyothi;Beg,Shaham;Wilkes,David;Robinson,BrianD;Kha
转移性上尿路上皮癌（UTUC）的分子特征还没有很好地理解，并且缺乏关于原发性和转移性UTUC之间基因组和转录组差异的知识。为了解决这些差距，我们整合了全外显子组测序，RNA测序和成像质谱细胞计数法，使用镧系金属偶联抗体的44个肿瘤样本，来自28例高级别原发性和转移性UTUC患者。我们对癌症、免疫细胞和基质细胞进行了空间分辨的单细胞分析，以了解原发性UTUC到转移性UTUC的演变。我们发现，在同一患者中，原发性和转移性UTUC肿瘤之间可操作的基因组改变经常不一致。相反，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中是稳定的。分子和免疫亚型在来自340，798个单细胞的蛋白标志物的批量RNA测序和质谱细胞术之间是一致的。在同一患者中原发性和转移性UTUC肿瘤之间，单细胞水平的分子亚型高度保守。
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.