Clinicopathological associations and prognostic values of IDH1 gene mutation, MGMT gene promoter methylation, and PD-L1 expressions in high-grade glioma treated with standard treatment.
Clinicopathological associations and prognostic values of IDH1 gene mutation, MGMT gene promoter methylation, and PD-L1 expressions in high-grade glioma treated with standard treatment.
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DOI：
10.11604/pamj.2020.36.309.24831
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Loe ML
中科院分区：
文献类型：
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作者：
July J;Patricia D;Gunawan PY;Setiajaya H;Ginting TE;Putra TP;Wuisan Z;Budhiarko D;Masykura N;Prayogi G;Utomo AR;Tandean S;Loe ML
目的是评估IDH1 R132H突变、MGMT甲基化和PD-L1表达对接受标准治疗（手术、放疗和化疗）的高级别胶质瘤患者总生存期（OS）的影响。本文是对35例高级别胶质瘤病例的回顾性研究。突变热点R132上IDH1基因改变的基因分型（应用Biosystems 3500 Genetic Analyzer的Sanger测序法），使用EZ DNA甲基化金试剂盒（Zymo Research）进行甲基化研究，分别以细胞系BT549 （ATCC HTB-122）和HCT-116 （ATCC CCL-247）作为未甲基化对照和部分甲基化对照。使用Cell signaling Technology （USA）公司和Rabbit XP®公司的抗人PD-L1抗体克隆E1L3N®检测PDL-1的表达。间变性星形细胞瘤患者MGMT启动子甲基化率（50%）高于多形性胶质母细胞瘤（GBM） （20%）， IDH1 R132H突变率（42%）高于GBM（4.3%）。免疫组化肿瘤比例评分法（TPS）显示，AA组和GBM组PD-L1阳性分别为17%和8.7%。IDH1 R132H突变和MGMT甲基化的患者虽然PD-L1表达较高，但仍表现出较好的OS。IDH1 R132H突变和MGMT甲基化是良好的预后指标。在IDH1 R132突变和MGMT甲基化的情况下，PD-L1的高表达显然并不意味着总生存率低。
the objective was to evaluate the impact of IDH1 R132H mutation, MGMT methylation and PD-L1 expression in high grade glioma that received standard therapy (surgery, radiation and chemotherapy) to overall survival (OS). this is a retrospective study of 35 high grade glioma cases. Genotyping of IDH1 gene alteration on the mutation hotspot R132 (Sanger sequencing method with Applied Biosystems 3500 Genetic Analyzer), EZ DNA Methylation-Gold kit (Zymo Research) is used to study the methylation, Cell line BT549 (ATCC HTB-122) and HCT-116 (ATCC CCL-247) were used as unmethylated control and partially methylated control respectively. Anti-human PD-L1 antibody clone E1L3N®from Cell Signalling Technology (USA) and Rabbit XP®were used to see PDL-1 expression. anaplastic astrocytoma cases had more MGMT promoter methylation (50%) than glioblastoma multiforme (GBM) (20%), more IDH1 R132H mutation (42%) than GBM (4.3%). Immunohistochemistry tumor proportion score method (TPS) identified 17% and 8.7% were PD-L1 positive in AA and GBM groups, respectively. Cases with IDH1 R132H mutation and MGMT methylation still showed better OS although with high PD-L1 expression. IDH1 R132H mutation and MGMT methylation were good prognostic markers. High expression of PD-L1 apparently might not indicate poor overall survival in the presence of IDH1 R132 mutation and MGMT methylation.