Gao Mengqi, Lin Yi, Liu Xing, Li Yiming, Zhang Chuanbao, Wang Zheng, Wang Zhiliang, Wang Yulin, Guo Zongze
Department of Neurosurgery, the First Hospital of China Medical University, Shenyang, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Oncoimmunology. 2018 Oct 31;8(2):e1534038. doi: 10.1080/2162402X.2018.1534038. eCollection 2019.
Recent evidence has confirmed that a mutation of the isocitrate dehydrogenase (IDH) gene occurs early in gliomagenesis and contributes to suppressed immunity. The present study aimed to determine the candidate genes associated with IDH mutation status that could serve as biomarkers of immune suppression for improved prognosis prediction. Clinical information and RNA-seq gene expression data were collected for 932 glioma samples from the CGGA and TCGA databases, and differentially expressed genes in both lower-grade glioma (LGG) and glioblastoma (GBM) samples were identified according to IDH mutation status. Only one gene, interferon-stimulated exonuclease gene 20 (ISG20), with reduced expression in IDH mutant tumors, demonstrated significant prognostic value. ISG20 expression level significantly increased with increasing tumor grade, and its high expression was associated with a poor clinical outcome. Moreover, increased ISG20 expression was associated with increased infiltration of monocyte-derived macrophages and neutrophils, and suppressed adaptive immune response. ISG20 expression was also positively correlated with PD-1, PD-L1, and CTLA4 expression, along with the levels of several chemokines. We conclude that ISG20 is a useful biomarker to identify IDH-mediated immune processes in glioma and may serve as a potential therapeutic target.
最近的证据证实，异柠檬酸脱氢酶（IDH）基因突变在胶质瘤发生早期就会出现，并导致免疫抑制。本研究旨在确定与IDH突变状态相关的候选基因，这些基因可作为免疫抑制的生物标志物，以改善预后预测。从CGGA和TCGA数据库收集了932例胶质瘤样本的临床信息和RNA测序基因表达数据，并根据IDH突变状态确定低级别胶质瘤（LGG）和胶质母细胞瘤（GBM）样本中的差异表达基因。只有一个基因，即干扰素刺激核酸外切酶基因20（ISG20），在IDH突变肿瘤中表达降低，具有显著的预后价值。ISG20表达水平随肿瘤分级增加而显著升高，其高表达与不良临床结局相关。此外，ISG20表达增加与单核细胞衍生的巨噬细胞和中性粒细胞浸润增加以及适应性免疫反应受抑制有关。ISG20表达还与PD-1、PD-L1和CTLA4表达以及几种趋化因子水平呈正相关。我们得出结论，ISG20是识别胶质瘤中IDH介导的免疫过程的有用生物标志物，可能作为潜在的治疗靶点。
