Genetic variants of m¹A modification genes and the risk of neuroblastoma: novel insights from a Chinese case-control study.

IF 3.8 3区医学 Q2 GENETICS & HEREDITY

Human Genomics Pub Date : 2025-05-08 DOI:10.1186/s40246-025-00767-0

Jiaming Chang, Lei Lin, Wenli Zhang, Jiliang Yang, Mengzhen Zhang, Huimin Yin, Xinxin Zhang, Chunlei Zhou, Yan Zou, Jing He

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引用次数: 0

Abstract

Background: The N¹-adenosine methylation (m¹A) modification plays a significant role in various cancers. However, the functions of m¹A modification genes and their variants in neuroblastoma remain to be elucidated.

Methods: We conducted a case-control study involving 402 neuroblastoma patients and 473 cancer-free controls from China via the TaqMan genotyping method to evaluate m¹A modification gene polymorphisms. Multivariate logistic regression analysis was conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Additionally, expression quantitative trait locus (eQTL) analysis utilizing the Genotype-Tissue Expression database was performed to investigate the impacts of significant polymorphisms on gene expression. The relationships between gene expression and the risk and prognosis of neuroblastoma patients were further examined via publicly available datasets by using the R2 platform.

Results: We found that TRMT10C rs4618204 C > T significantly decreased neuroblastoma risk (CT/TT vs. CC: adjusted OR = 0.74, 95% CI = 0.56-0.97, P = 0.030). Moreover, polymorphisms of the TRMT10C (rs3762735), TRMT6 (rs451571 and rs236110), and ALKBH3 (rs10768993 and rs2292889) genes were associated with neuroblastoma risk in specific subgroups. Complete linkage disequilibrium and eQTL analysis revealed a significant association between rs4618204 C > T and reduced expression of the TRMT10C gene. Additionally, higher expression levels of the TRMT10C gene were observed to be linked to increased risk, malignancy, and poorer prognosis in neuroblastoma patients.

Conclusions: TRMT10C rs4618204 C > T was demonstrated to be significantly associated with an increased risk of neuroblastoma and may serve as a potential molecular marker for early diagnosis. Further studies are warranted to fully elucidate the specific molecular mechanisms involved in this effect.

Clinical trial number: Not applicable.

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m1A修饰基因的遗传变异与神经母细胞瘤的风险：来自中国病例对照研究的新见解

背景：n1 -腺苷甲基化（m1A）修饰在多种癌症中起重要作用。然而，m1A修饰基因及其变异在神经母细胞瘤中的功能仍有待阐明。方法：采用TaqMan基因分型方法，对402例神经母细胞瘤患者和473例无癌对照进行病例对照研究，评估m1A修饰基因多态性。进行多因素logistic回归分析以估计优势比（ORs）和95%置信区间（ci）。此外，利用基因型-组织表达数据库进行表达数量性状位点（eQTL）分析，研究显著多态性对基因表达的影响。基因表达与神经母细胞瘤患者的风险和预后之间的关系通过R2平台通过公开的数据集进一步检查。结果：我们发现TRMT10C rs4618204 C > T显著降低神经母细胞瘤的风险（CT/TT vs. CC：校正OR = 0.74, 95% CI = 0.56-0.97, P = 0.030）。此外，在特定亚组中，TRMT10C （rs3762735）、TRMT6 （rs451571和rs236110）和ALKBH3 （rs10768993和rs2292889）基因多态性与神经母细胞瘤风险相关。完全连锁不平衡和eQTL分析显示rs4618204 C > T与TRMT10C基因表达降低之间存在显著关联。此外，观察到TRMT10C基因的高表达水平与神经母细胞瘤患者的风险增加、恶性肿瘤和预后较差有关。结论：TRMT10C rs4618204 C > T被证明与神经母细胞瘤风险增加显著相关，可能作为早期诊断的潜在分子标志物。需要进一步的研究来充分阐明这种作用的具体分子机制。临床试验号：不适用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Genomics GENETICS & HEREDITY-

CiteScore

6.00

自引率

2.20%

发文量

审稿时长

11 weeks

期刊介绍： Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.