NEUROD1靶基因的遗传变异与小细胞肺癌患者的临床结果相关。
Genetic variants of NEUROD1 target genes are associated with clinical outcomes of small-cell lung cancer patients.
发表日期：2023 Mar 19
作者：
Sunwoong Lee, Seung Soo Yoo, Jin Eun Choi, Mi Jeong Hong, Sook Kyung Do, Jang Hyuck Lee, Won Ki Lee, Ji Eun Park, Sun Ha Choi, Hyewon Seo, Jaehee Lee, Shin Yup Lee, Seung Ick Cha, Chang Ho Kim, Hyo-Gyoung Kang, Jae Yong Park
来源：
Cellular & Molecular Immunology
摘要：
神经元分化因子1（NEUROD1）在小细胞肺癌（SCLC）中经常表达过多。NEUROD1在促进恶性行为和生存方面发挥重要作用。在这项研究中，我们评估了261名SCLC患者45个NEUROD1靶基因假定功能多态性与化疗反应和生存结果之间的关联。在研究的100个单核苷酸多态性（SNP）中，有两个与SCLC患者的化疗反应和总生存期（OS）具有显著关联。SEMA6A基因的rs3806915C>A SNP与更好的化疗反应和OS（p = 0.04和p = 0.04，分别）显著相关。nescient螺旋-环-螺旋1（NHLH1）基因的rs11265375C>T SNP也与更好的化疗反应和OS（p = 0.04和p = 0.02，分别）相关。Luciferase测定显示，与C等位基因相比，在H446肺癌细胞中，rs3806915A等位基因的SEMA6A更高的启动子活性显著（p = 4×10-6）。与C等位基因相比，NHLH1的启动子活性显示出rs11265375T等位基因显着更高（p = 0.001）。这些结果表明SEMA6A rs3806915C>A和NHLH1 rs11265375C>T多态性影响基因的启动子活性和表达，可能会影响SCLC患者的生存结果。©2023作者。中国肺癌学组和John Wiley＆Sons Australia，Ltd.出版并发表于《胸腔肿瘤》。
Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small-cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival.In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC.The SNP rs3806915C⟩A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (p = 0.04 and p = 0.04, respectively). The SNP rs11265375C⟩T in nescient helix-loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (p = 0.04 and p = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (p = 4 × 10-6 ). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (p = 0.001).These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC.© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.