A genetic variant in the immune-related gene ERAP1 affects colorectal cancer prognosis / 中华医学杂志(英文版)
Chin. med. j
; Chin. med. j;(24): 431-440, 2024.
Article
em En
| WPRIM
| ID: wpr-1007678
Biblioteca responsável:
WPRO
ABSTRACT
BACKGROUND@#Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.@*METHODS@#We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.@*RESULTS@#The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1 ) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1 . The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.@*CONCLUSION@#The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1 .@*TRIAL REGISTRATION@#No. NCT00454519 ( https://clinicaltrials.gov/ ).
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Prognóstico
/
Neoplasias Colorretais
/
Antígenos de Histocompatibilidade Menor
/
Polimorfismo de Nucleotídeo Único
/
Locos de Características Quantitativas
/
Microambiente Tumoral
/
Genótipo
/
Aminopeptidases
Limite:
Humans
Idioma:
En
Revista:
Chin. med. j
Ano de publicação:
2024
Tipo de documento:
Article