Promoter-Specific Variants in NeuroD1 and H3K4me3 Coincident Regions and Clinical Outcomes of Small Cell Lung Cancer.
J Korean Med Sci
; 38(45): e381, 2023 Nov 20.
Article
em En
| MEDLINE
| ID: mdl-37987107
ABSTRACT
BACKGROUND:
Neurogenic differentiation 1 (NeuroD1) is a representative small cell lung cancer (SCLC) transcription regulator involved in the carcinogenesis and behavior of SCLC. Histone modifications play an important role in transcription, and H3 lysine 4 trimethylation (H3K4me3) is primarily associated with promoter regions.METHODS:
We investigated the association between single nucleotide polymorphisms (SNPs) in NeuroD1 and H3K4me3 coincident regions, selected using ChIP sequencing (ChIP-seq), and the clinical outcomes of 261 patients with SCLC.RESULTS:
Among 230 SNPs, two were significantly associated with both the chemotherapy response and overall survival (OS) of patients with SCLC. RNF145 rs2043268A>G was associated with worse chemotherapy response and OS (under a recessive model, adjusted odds ratio [aOR], 0.50, 95% confidence interval [CI], 0.26-0.94, P = 0.031, and adjusted hazard ratio [aHR], 1.88, 95% CI, 1.38-2.57, P < 0.001). CINP rs762105A>G was also associated with worse chemotherapy response and OS (under a dominant model, aOR, 0.47, 95% CI, 0.23-0.99, P = 0.046, and aHR, 2.03, 95% CI, 1.47-2.82, P < 0.001). ChIP-quantitative polymerase chain reaction and luciferase assay confirmed that the two SNPs were located in the active promoter regions and influenced the promoter activity of each gene.CONCLUSION:
To summarize, among SNPs selected using ChIP-seq in promoter regions with high peaks in both NeuroD1 and H3K4me3, RNF145 rs2043268A>G and CINP rs762105A>G were associated with clinical outcomes in patients with SCLC and also affected the promoter activity of each gene.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Pequenas Células do Pulmão
/
Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article