成人胶质母细胞瘤TERT启动子和ATRX突变预后价值

Prognostic value of TERT promoter and ATRX mutations in adult glioblastoma

目的探究成人胶质母细胞瘤(glioblastoma,GBM)中端粒酶逆转录酶(telomerase reverse transcriptase,TERT)启动子,α-地中海贫血伴智力低下综合征基因(alpha-thalassemia/mental retardation syndrome X-linked,ATRX)突变对预后的影响。方法收集2020年至2022年在徐州医科大学附属医院神经外科行手术治疗的82例GBM患者病理及随访资料。TERT启动子区(C228T和C250T)及ATRX突变检测采用多重PCR扩增+二代测序(next generation sequencing,NGS)方法,根据患者HE染色切片的镜下结果将其分为低级别组织形态的GBM和高级别组织形态GBM两组,分析两组GBM患者TERT启动子和ATRX突变率的差异。GBM患者预后的影响因素采用多因素COX回归分析。结果两组GBM患者中TERT启动子突变率(25.0%vs.75.8%,χ^(2)=12.584,P<0.01)存在统计学差异。年龄≤60岁、术中肿瘤全切、术后放疗、化疗、TERT启动子非突变是影响GBM患者预后的独立保护性因素(P<0.05)。结论TERT启动子突变的GBM患者预后较差、临床中常规检测TERT启动子并结合其他分子标记物有助于正确评估GBM患者预后,有较高临床价值。

Objective To investigate the prognostic effect of mutations in theα-thalassemia with mental retardation syndrome gene(ATRX)and the telomerase reverse transcriptase(TERT)promoter in glioblastoma(GBM)among adult individuals.Methods The present study collected the pathological and follow-up data of a cohort including 82 patients with glioblastoma multiforme(GBM)who received treatment at the Neurosurgery Department of the Affiliated Hospital of Xuzhou Medical University between 2020 and 2022.TERT promoter region(C228T and C250T)and ATRX mutation was detected using a multiplex PCR amplification followed by next-generation sequencing(NGS).The samples were categorized into two groups based on the high-grade tissue morphology in the HE stained sections:GBM with low-grade tissue morphology and those with high-grade tissue morphology.The Comparative analysis was used to examine the differences in mutation rates of TERT promoter and ATRX between the two groups.The multivariate COX regression analysis was conducted to examine the prognostic characteristics among patients with glioblastoma(GBM)multiforme.Results The TERT promoter mutation rate was significantly different(25.0%vs.75.8%,χ^(2)=12.584,P<0.01)in the two groups of GBM patients.Age≤60 years,total tumor resection,postoperative radiotherapy,chemotherapy and TERT promoter non-mutation were independent protective factors affecting the prognosis of GBM patients(P<0.05).Conclusion GBM patients with TERT promoter mutation have poor prognosis,and routine detection of TERT promoter combined with other molecular markers can help to precisely assess the prognosis of GBM patients,which has high clinical value.