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KMID : 0191120230380450381
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Journal of Korean Medical Science
2023 Volume.38 No. 45 p.381 ~ p.381
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Promoter-Specific Variants in NeuroD1 and H3K4me3 Coincident Regions and Clinical Outcomes of Small Cell Lung Cancer
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Yoo Seung-Soo
Lee Sun-Woong
Choi Jin-Eun
Hong Mi-Jeong
Do Sook-Kyung
Lee Jang-Hyuck
Lee Won-Kee
Park Ji-Eun
Lee Yong-Hoon
Choi Sun-Ha
Seo Hye-Won
Lee Jae-Hee
Lee Shin-Yup
Cha Seung-Ick
Kim Chang-Ho
Kang Hyo-Gyoung
Park Jae-Yong
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Abstract
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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.
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KEYWORD
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NeuroD1, H3K4me3, Small Cell Lung Cancer, Variant, ChIP-seq
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