Mutations in the notch signalling pathway are associated with enhanced anti-tumour immunity in colorectal cancer.
J Cell Mol Med
; 24(20): 12176-12187, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32924269
ABSTRACT
The Notch signalling pathway is involved in the development of several cancers, including colorectal cancer (CRC). However, whether mutations in this pathway could alter the CRC immunophenotype remains unknown. Here, we investigated the relationship between Notch signalling pathway mutations and the tumour immune microenvironment by analysing gene expression data from the GSE108989 single T cell RNA sequencing data set and The Cancer Genome Atlas (TCGA) data set. We found that Notch signalling pathway mutations were associated with an increased number of tumour-specific CD8+ T cells and decreased number of inhibitory regulatory T (Treg) cells, representing an enhanced anti-tumour response in the GSE108989 data set. In TCGA data set, we also found that Notch signalling pathway mutations were associated with enrichment of genes associated with immune activation pathways and higher expressions of PDCD1, GZMB and PRF1. Although Notch signalling pathway mutations did not affect the overall survival and disease-free survival of CRC patients, they were associated with earlier disease stages and lower rates of metastasis. These results demonstrated that Notch signalling pathway mutations can enhance anti-tumour immunity in CRC, as validated by the two data sets, suggesting that they may be promising biomarkers for immune checkpoint blockade therapies for CRC patients.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Transducción de Señal
/
Receptores Notch
/
Inmunidad
/
Mutación
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Cell Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2020
Tipo del documento:
Article
País de afiliación:
China