The integrate profiling of single-cell and spatial transcriptome RNA-seq reveals tumor heterogeneity, therapeutic targets, and prognostic subtypes in ccRCC.
Cancer Gene Ther
; 31(6): 917-932, 2024 Jun.
Article
de En
| MEDLINE
| ID: mdl-38480978
ABSTRACT
Clear-cell renal cell carcinoma (ccRCC) is the most common type of RCC; however, the intratumoral heterogeneity in ccRCC remains unclear. We first identified markers and biological features of each cell cluster using bioinformatics analysis based on single-cell and spatial transcriptome RNA-sequencing data. We found that gene copy number loss on chromosome 3p and amplification on chromosome 5q were common features in ccRCC cells. Meanwhile, NNMT and HILPDA, which are associated with the response to hypoxia and metabolism, are potential therapeutic targets for ccRCC. In addition, CD8+ exhausted T cells (LAG3+ HAVCR2+), CD8+ proliferated T cells (STMN+), and M2-like macrophages (CD68+ CD163+ APOC1+), which are closely associated with immunosuppression, played vital roles in ccRCC occurrence and development. These results were further verified by whole exome sequencing, cell line and xenograft experiments, and immunofluorescence staining. Finally, we divide patients with ccRCC into three subtypes using unsupervised cluster analysis. and generated a classifier to reproduce these subtypes using the eXtreme Gradient Boosting algorithm. Our classifier can help clinicians evaluate prognosis and design personalized treatment strategies for ccRCC. In summary, our work provides a new perspective for understanding tumor heterogeneity and will aid in the design of antitumor therapeutic strategies for ccRCC.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Néphrocarcinome
/
Analyse sur cellule unique
/
Tumeurs du rein
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Cancer Gene Ther
Sujet du journal:
GENETICA MEDICA
/
NEOPLASIAS
/
TERAPEUTICA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Royaume-Uni