Title | The evolution of metastatic upper tract urothelial carcinoma through genomic-transcriptomic and single-cell protein markers analysis. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Ohara K, Rendeiro AFigueiredo, Bhinder B, Eng KWha, Ravichandran H, Nguyen D, Pisapia D, Vosoughi A, Fernandez E, Shohdy KS, Manohar J, Beg S, Wilkes D, Robinson BD, Khani F, Bareja R, Tagawa ST, Ouseph MM, Sboner A, Elemento O, Faltas BM, Mosquera JMiguel |
Journal | Nat Commun |
Volume | 15 |
Issue | 1 |
Pagination | 2009 |
Date Published | 2024 Mar 18 |
ISSN | 2041-1723 |
Keywords | Carcinoma, Transitional Cell, Gene Expression Profiling, Genomics, Humans, Transcriptome, Urinary Bladder Neoplasms |
Abstract | 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. |
DOI | 10.1038/s41467-024-46320-w |
Alternate Journal | Nat Commun |
PubMed ID | 38499531 |
PubMed Central ID | PMC10948878 |
Grant List | T32CA203702 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) / |
Related Faculty:
Andrea Sboner, Ph.D. Brian Robinson, M.D. David Pisapia, M.D. Francesca Khani, M.D. Juan Miguel Mosquera, M.D. Madhu Ouseph, M.D., Ph.D.