Characterization and impact of non-canonical WNT signaling on outcomes of urothelial carcinoma.
Cancer Med
; 13(7): e7148, 2024 Apr.
Article
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| MEDLINE
| ID: mdl-38558536
ABSTRACT
BACKGROUND:
Non-canonical WNT family (WNT5A pathway) signaling via WNT5A through ROR1 and its partner, ROR2, or Frizzled2 (FZD2) is linked to processes driving tumorigenesis and therapy resistance. We utilized a large dataset of urothelial carcinoma (UC) tumors to characterize non-canonical WNT signaling through WNT5A, ROR1, ROR2, or FZD2 expression.METHODS:
NextGen Sequencing of DNA (592 genes or WES)/RNA (WTS) was performed for 4125 UC tumors submitted to Caris Life Sciences. High and low expression of WNT5A, ROR1, ROR2, and FZD2 was defined as ≥ top andRESULTS:
WNT5A pathway gene expression varied significantly between primary versus metastatic sites WNT5A (25.2 vs. 16.8 TPM), FZD2 (3.2 vs. 4.05), ROR1 (1.7 vs. 2.1), and ROR2 (2.4 vs. 2.6) p < 0.05 for all. Comparison of high- and low-expression subgroups revealed variation in the prevalence of TP53, FGFR3, and RB1 pathogenic mutations, as well as increasing T cell-inflamed scores as expression of the target gene increased. High gene expression for ROR2 (HR 1.31, 95% CI 1.15-1.50, p < 0.001) and FZD2 (HR 1.16, 95% CI 1.02-1.32, p = 0.024) was associated with worse OS.CONCLUSION:
Distinct genomic and immune landscapes for the four investigated WNT5A pathway components were observed in patients with UC. External validation studies are needed.Palabras clave
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Vejiga Urinaria
/
Carcinoma de Células Transicionales
Límite:
Humans
Idioma:
En
Revista:
Cancer Med
/
Cancer med
/
Cancer medicine
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos