星形细胞瘤4级患者临床病理特征及生物信息学分析
The Clinic-pathological Characteristics and Bioinformatics Analysis of IDH-mutant Grade 4 Astrocytoma
刘晓佳 1陈诗雨 1程海霞 1陈宏1
作者信息
- 1. 复旦大学附属华山医院病理科,上海 200040
- 折叠
摘要
目的 探讨WHO 4级IDH突变型星形细胞瘤的临床病理学特征.方法 收集2021至2023年诊断为WHO 4级IDH突变型星形细胞瘤患者的临床资料,观察组织学及免疫表型,检测相关分子病理指标,进行临床病理相关性分析;利用生物信息学方法筛选高级别星形细胞瘤预后相关基因.结果 本研究共入组WHO 4级星形细胞瘤患者(AG4)140例,包括100例首发患者(pAG4组)和40例继发患者(sAG4组).95.7％(134/140例)病例可由组织学直接诊断AG4,CDKN2A/B纯合性缺失率约为8.6％(12/140例);20.7％(29/140例)sAG4患者初次手术组织学诊断为2级.pAG4及sAG4的诊断条件均包括血管内皮增生、坏死、CDKN2A/B纯合性缺失单独一项或者任意组合.免疫组化检测显示ATRX、TP53突变率高,且sAG4的突变率高于pAG4;Ki-67表达具有个体差异(为10％～35％).测序结果显示IDH的突变类型中IDH1 p.R132H突变最为常见.预后分析显示sAG4第一次发病时级别越高,进展为4级的时间越短;首诊为AG2的患者接受规范治疗可以延长复发/进展时间.通过生信分析筛选到差异表达基因GLUD1和GLUD2,其在星形细胞瘤中的表达明显高于胶质母细胞瘤,提示较低的复发率和较长的总生存期.结论 pAG4和sAG4患者的生物学行为不尽相同.AG4形态多样,需与少突胶质细胞瘤、胶质母细胞瘤、原始神经外胚层肿瘤等鉴别,R132H突变为最常见的IDH突变类型.同步放、化疗能够延长术后复发/进展时间.GLUD1/GLUD2基因在胶质瘤中的高表达提示较低的复发率和较长的总生存期.
Abstract
Aim To explore the clinical and pathological characteristics of WHO grade 4 IDH mutant astrocytoma.Methods Clinical data of patients diagnosed as WHO grade 4 IDH mutant astrocytoma by the department of pathology,Huashan Hospital from 2021 to 2023 was collected.Their histology and immune phenotype were observed,molecular pathological indexes were detected,and clinic pathological correlation was analyzed.The prognostic genes of high-grade astrocytoma were screened by bioinformatics method.Results A total of 140 patients with WHO grade 4 astrocytoma(grade 4,AG4)were enrolled in this study,including 100 primary astrocytoma,grade 4(pAG4)and 40 secondary astrocytoma,grade 4(sAG4).95.7％(134/140)patients could be diagnosed as AG4 by histology directly,and the homozygous deletion rate of CDKN2A/B was 8.6％(12/140);20.7％(29/144)of sAG4 patients had a histological diagnosis of grade 2 initially.The diagnostic criteria for pAG4 and sAG4 included endothelial proliferation,necrosis,or CDKN2A/B homozygous loss alone or in any combination.Immunohistochemical tests showed that the mutation rates of ATRX and TP53 in sAG4 were higher than those in pAG4.Ki-67 showed diversity ranging from 10％to 35％.The sequencing results showed that IDH1 p.R132H mutation was the most common type of IDH mutation.The analysis of patient prognosis in this study showed that the higher the level of astrocytoma at the initial diagnosis,the shorter the time of relapse or upgrading.Patients with initial diagnosis of AG2 receiving standardized treatment could prolong the recurrence time.In addition,the differentially expressed genes GLUD1 and GLUD2 were screened through bioinformatics analysis.Their expression in astrocytoma was significantly higher than that in glioblastoma,indicating a lower recurrence rate and longer overall survival(OS).Conclusion pAG4 and sAG4 had different biological behaviors.AG4 has various morphological characters and needs to be distinguished from oligodendroglioma,glioblastoma,primitive neuroectodermal tumor,etc.R132H mutation was the most common mutation type of IDH.Synchronous radiotherapy and chemotherapy could prolong the postoperative recurrence/escalation.Higher expression of differentially expressed genes GLUD1 and GLUD2 in gliomas suggested a lower recurrence rate and longer OS,and the internal mechanism needs to be explored.
关键词
星形细胞瘤/IDH突变/CDKN2A/B/复发/预后/GLUD1/GLUD2/生物信息学分析Key words
astrocytoma/IDH mutation/CDKN2A/B/recurrence/prognosis/GLUD1/GLUD2/bioinformatics analysis引用本文复制引用
基金项目
科技部科技创新2030-脑科学与类脑研究项目(2021ZD0201100)
科技部科技创新2030-脑科学与类脑研究项目(2021ZD0201104)
&&(KY2019-539)
国家自然科学基金(81902834)
出版年
2024
NETL
NSTL
万方数据