脑胶质瘤患者SEL1L基因多态性与总生存率和替莫唑胺敏感性的关系

doi:10.19854/j.cnki.1008-2425.2024.04.0003

立体定向和功能性神经外科杂志 ›› 2024, Vol. 37 ›› Issue (4): 205-209.DOI: 10.19854/j.cnki.1008-2425.2024.04.0003

脑胶质瘤患者SEL1L基因多态性与总生存率和替莫唑胺敏感性的关系

彭超, 陈宇澄, 张之娟, 廖黎庆

433100 潜江潜江市中心医院神经外科

收稿日期:2024-04-18 出版日期:2024-08-25 发布日期:2024-11-12
通讯作者: 廖黎庆 53911358@qq.com
基金资助:
潜江市公益性行业科研计划项目(编号:2021GYX005)

Relationship between SEL1L gene polymorphism and overall survival and temozolomide sensitivity in glioma

Peng Chao, Chen Yucheng, Zhang Zhijuan, Liao Liqing

Department of Neurosurgery, Qianjiang Central Hospital, Qianjiang, 433100, China

Received:2024-04-18 Online:2024-08-25 Published:2024-11-12
Contact: Liao Liqing 53911358@qq.com

摘要/Abstract

摘要： 目的本研究旨在分析脑胶质瘤患者Lin-12样(秀丽隐杆线虫)(Caenorhabditis elegans,SEL1L)抑制基因多态性与总生存率和替莫唑胺(temozolomide,TMZ)敏感性的关系。方法 2019年1月至2023年1月间共招募了66名经病理证实的神经胶质瘤患者,包括32例胶质母细胞瘤(glioblastoma,GBM)和34例低级别脑胶质瘤(low grade glioma,LGG)。所有患者术后均接受TMZ辅助化疗和/或放疗。肿瘤组织O-6-甲基鸟嘌呤-DNA甲基转移酶(O-6-methylguanine-DNA methyltransferase,MGMT)启动子甲基化通过亚硫酸氢盐转化和焦磷酸测序来测量,通过SNaPShot^TM测定法确定了肿瘤组织和外周血单核细胞(对照样本)SEL1L内含子3中rs12435998单核苷酸遗传变异的频率。随访患者总生存期(OST)。结果 rs12435998次要等位基因G在肿瘤样本中的等位基因频率为19.70%(26/132),在对照样本中仅为9.85%(13/132)。GBM患者AG/GG基因型比例明显更高(P=0.047),另外,肿瘤组织rs12435998基因型与对照样本rs12435998基因型趋势相匹配。肿瘤rs12435998基因型与GBM患者(P=0.520)或MGMT超甲基化患者(P=0.299)的OST无关。但是rs12435998AG/GG基因型的LGG患者中位OST更短(17.10个月 vs.53.20个月)(HR:6.844;95%CI:1.991~23.530;P=0.002)。同样,对于MGMT低甲基化患者,肿瘤rs12435998AG/GG基因型患者中位OST短于AA基因型患者(7.10个月 vs.44.80个月)(HR:2.937;95%CI:1.155~7.464;P=0.024)。结论 SEL1L rs12435998基因多态性可能是LGG的一种新的分子分层,其G次等位基因与较差的TMZ敏感性和生存预后有关。

关键词: 脑胶质瘤, Lin-12样(秀丽隐杆线虫)抑制基因, 替莫唑胺, 低级别脑胶质瘤, 总生存期

Abstract: Objective To investigate the relationship between Lin-12-like (C.elegans) (SEL1L) suppressant gene polymorphism and overall survival or temozolomide (TMZ) sensitivity in patients with glioma. Methods A total of 66 patients with pathologically confirmed glioma,including 32 cases of glioblastoma (GBM) and 34 cases of low-grade glioma (LGG),were enrolled between January 2019 and January 2023.All patients received TMZ adjuvant chemotherapy and/or radiotherapy after surgery.Tumor tissue O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation was measured by bisulfite transformation and pyrosequencing,and the frequency of rs12435998 single nucleotide genetic variation in SEL1L intron 3 in tumor tissue and peripheral blood mononuclear cells (control samples) was determined by SNaPShot^TM assays.Overall survival (OST) was followed up. Results The allele frequency of rs12435998 minor allele G was 19.70% (26/132) in tumor samples,but only 9.85% (13/132) in control samples.The proportion of AG/GG genotypes in GBM patients was significantly higher (P=0.047).In addition,the rs12435998 genotype in tumor tissue matched the rs12435998 genotype trend in control sample.Tumor rs12435998 genotype was not associated with OST in patients with GBM (P=0.520) or MGMT hypermethylation (P=0.299).However,LGG patients with rs12435998AG/GG genotype had a shorter median OST (17.10 months vs.53.20 months) (HR:6.844;95%CI:1.991~23.530;P=0.002).Similarly,for MGMT hypomethylation patients,the median OST in patients with tumor rs12435998AG/GG genotype was shorter than that in patients with AA genotype (7.10 months vs.44.80 months) (HR:2.937;95%CI:1.155~7.464;P=0.024). Conclusion SEL1L rs12435998 gene polymorphism may be a new molecular stratification of LGG,and its G suballele is associated with poor TMZ sensitivity and survival prognosis.

Key words: Brain glioma, Lin-12-like (C.elegans) suppressor gene, Temozolomide, Low grade brain glioma, Overall survival

中图分类号:

R739.4

彭超, 陈宇澄, 张之娟, 廖黎庆. 脑胶质瘤患者SEL1L基因多态性与总生存率和替莫唑胺敏感性的关系[J]. 立体定向和功能性神经外科杂志, 2024, 37(4): 205-209.

Peng Chao, Chen Yucheng, Zhang Zhijuan, Liao Liqing. Relationship between SEL1L gene polymorphism and overall survival and temozolomide sensitivity in glioma[J]. Chinese Journal of Stereotactic and Functional Neurosurgery, 2024, 37(4): 205-209.

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脑胶质瘤患者SEL1L基因多态性与总生存率和替莫唑胺敏感性的关系

Relationship between SEL1L gene polymorphism and overall survival and temozolomide sensitivity in glioma

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