Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer.
Oncology
; 99(5): 336-344, 2021.
Article
em En
| MEDLINE
| ID: mdl-33626541
ABSTRACT
BACKGROUND:
Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery.METHODS:
A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http//galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated.RESULTS:
Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00-1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46-0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes.CONCLUSIONS:
In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Carcinoma Pulmonar de Células não Pequenas
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Polimorfismo de Nucleotídeo Único
/
Proteínas Adaptadoras de Transdução de Sinal
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Fator 3 Ativador da Transcrição
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Álcool Oxidorredutases Dependentes de NAD(/) e NADP(/)
/
Neoplasias Pulmonares
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Oncology
Ano de publicação:
2021
Tipo de documento:
Article