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

作　　者：彭超 陈宇澄[1] 张之娟 廖黎庆 Peng Chao;Chen Yucheng;Zhang Zhijuan;Liao Liqing(Department of Neurosurgery,Qianjiang Central Hospital,Qianjiang,433100,China)

机构地区：[1]潜江市中心医院神经外科,潜江433100

出　　处：《立体定向和功能性神经外科杂志》2024年第4期205-209,216,共6页Chinese Journal of Stereotactic and Functional Neurosurgery

基　　金：潜江市公益性行业科研计划项目(编号:2021GYX005)。

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。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.

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 

分 类 号：R739.4[医药卫生—肿瘤]