Chang Jiaming, Lin Lei, Zhang Wenli, Yang Jiliang, Zhang Mengzhen, Yin Huimin, Zhang Xinxin, Zhou Chunlei, Zou Yan, He Jing
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, China.
Department of Pathology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, Jiangsu, China.
Hum Genomics. 2025 May 8;19(1):50. doi: 10.1186/s40246-025-00767-0.
The N-adenosine methylation (mA) modification plays a significant role in various cancers. However, the functions of mA modification genes and their variants in neuroblastoma remain to be elucidated.
We conducted a case-control study involving 402 neuroblastoma patients and 473 cancer-free controls from China via the TaqMan genotyping method to evaluate mA 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.
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.
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.
Not applicable.
N-腺苷甲基化（mA）修饰在多种癌症中发挥重要作用。然而，mA修饰基因及其变体在神经母细胞瘤中的功能仍有待阐明。
我们通过TaqMan基因分型方法对402例中国神经母细胞瘤患者和473例无癌对照进行了病例对照研究，以评估mA修饰基因多态性。进行多因素逻辑回归分析以估计比值比（OR）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定量性状位点（eQTL）分析，以研究显著多态性对基因表达的影响。通过使用R2平台，通过公开可用数据集进一步研究基因表达与神经母细胞瘤患者风险和预后之间的关系。
我们发现TRMT10C rs4618204 C>T显著降低神经母细胞瘤风险（CT/TT与CC相比：调整后OR=0.74，95%CI=0.56-0.97，P=0.030）。此外，TRMT10C（rs3762735）、TRMT6（rs451571和rs236110）和ALKBH3（rs10768993和rs2292889）基因的多态性在特定亚组中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基因的较高表达水平与神经母细胞瘤患者的风险增加、恶性程度和较差预后相关。
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。有必要进一步研究以充分阐明这种效应所涉及的具体分子机制。
不适用。
