Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression.
Nat Genet
; 56(3): 442-457, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-38361033
ABSTRACT
Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Renales
/
Neoplasias Renales
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Genet
/
Nat. genet
/
Nature genetics
Asunto de la revista:
GENETICA MEDICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos