The evolution of metastatic upper tract urothelial carcinoma through genomic-transcriptomic and single-cell protein markers analysis.
Kentaro OharaAndré Figueiredo RendeiroBhavneet BhinderKenneth Wha EngHiranmayi RavichandranDuy NguyenDavid PisapiaAram VosoughiEvan FernandezKyrillus S ShohdyJyothi ManoharShaham BegDavid C WilkesBrian D RobinsonFrancesca KhaniRohan BarejaScott T TagawaMadhu M OusephAndrea SbonerOlivier ElementoBishoy Morris FaltasJuan-Miguel MosqueraPublished in: Nature communications (2024)
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.
Keyphrases
- single cell
- squamous cell carcinoma
- rna seq
- small cell lung cancer
- high throughput
- high grade
- healthcare
- magnetic resonance
- induced apoptosis
- magnetic resonance imaging
- gene expression
- high resolution
- transcription factor
- mass spectrometry
- computed tomography
- photodynamic therapy
- oxidative stress
- copy number
- cell proliferation
- lymph node metastasis
- protein protein
- pi k akt