Promoter-Specific Variants in NeuroD1 and H3K4me3 Coincident Regions and Clinical Outcomes of Small Cell Lung Cancer
10.3346/jkms.2023.38.e381
- Author:
Seung Soo YOO
1
;
Sunwoong LEE
;
Jin Eun CHOI
;
Mi Jeong HONG
;
Sook Kyung DO
;
Jang Hyuck LEE
;
Won Kee LEE
;
Ji Eun PARK
;
Yong Hoon LEE
;
Sun Ha CHOI
;
Hyewon SEO
;
Jaehee LEE
;
Shin Yup LEE
;
Seung Ick CHA
;
Chang Ho KIM
;
Hyo-Gyoung KANG
;
Jae Yong PARK
Author Information
1. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
- Publication Type:Original Article
- From:Journal of Korean Medical Science
2023;38(45):e381-
- CountryRepublic of Korea
- Language:English
-
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.
