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基于异丙酚和七氟醚麻醉的共表达预后相关基因标志物预测胶质母细胞瘤的预后和免疫治疗反应。

Co-expression prognostic-related genes signature base on propofol and sevoflurane anesthesia predict prognosis and immunotherapy response in glioblastoma.

机构信息

Hui Zhou Central People's Hospital, HuiZhou, Guangdong, China.

Department of Anesthesiology, Hui Dong County People's Hospital, HuiZhou, Guangdong, China.

出版信息

Ann Med. 2023 Dec;55(1):778-792. doi: 10.1080/07853890.2023.2171109.

Abstract

OBJECTIVES

Anesthetic drugs had been reported may impact the bio-behavior of the tumor. Propofol and sevoflurane are common anesthetics in the operation for glioblastoma (GBM). This study aims to establish a co-expression prognostic-related genes signature base on propofol and sevoflurane anesthesia to predict prognosis and immunotherapy response in GBM.

METHOD

GPM tissues with different anesthetics gene expression profiles (GSE179004) were obtained from the Gene Expression Omnibus (GEO) database. Core modules and central genes associated with propofol and sevoflurane anesthesia were identified by weighted gene coexpression network analysis (WGCNA) and establish a risk score prognostic model. Immune cell signature analysis in TCGA datasets was predicted via CIBERSORT. At last, serum methylation level of O6-methylguanine-DNA methyltransferase (MGMT) promoter was detected in GPM patient in different time during perioperative period.

RESULTS

The burlywood1 group screened was significantly associated with sevoflurane-treated GBM tissue. 22 independent prognostic differential genes were construct a prognostic-related genes risk score in GBM, and showed good predictive ability. The risk score was strongly correlated with the age of the patients, but not with the sex of the patients. In addition, the differential responses to immunotherapy in high and low risk groups were analyzed, indicating that sevoflurane signature genes were consistent in the classification of gliomas. High-risk patients have high T-cell damage score and are less sensitive to immunotherapy. At last, serum methylation level of MGMT promoter was decreased in GBM patients during propofol and sevoflurane anesthesia.

CONCLUSIONS

Propofol and sevoflurane anesthesia associated impact on the gene expression of GBM, included the methylation level of MGMT promoter. Propofol and sevoflurane anesthesia-based risk score prognostic model, which has good prognostic power and is an independent prognostic factor in GBM patients. Therefore, this model can be used as a new biomarker for judging the prognosis of GBM patients.KEY MESSAGESPropofol and sevoflurane anesthesia-based risk score prognostic model has good prognostic power and is an independent prognostic factor in GBM patients.High Propofol and sevoflurane anesthesia-based risk score GBM patients have high T-cell damage scores and are less sensitive to immunotherapy.Serum methylation level of MGMT promoter decrease during propofol and sevoflurane anesthesia in GBM patients.

摘要

目的

有报道称麻醉药物可能会影响肿瘤的生物行为。丙泊酚和七氟醚是胶质母细胞瘤(GBM)手术中常用的麻醉剂。本研究旨在建立基于丙泊酚和七氟醚麻醉的共表达预后相关基因特征签名,以预测 GBM 的预后和免疫治疗反应。

方法

从基因表达综合数据库(GEO)中获得具有不同麻醉基因表达谱的 GPM 组织(GSE179004)。通过加权基因共表达网络分析(WGCNA)确定与丙泊酚和七氟醚麻醉相关的核心模块和核心基因,并建立风险评分预后模型。通过 CIBERSORT 预测 TCGA 数据集的免疫细胞特征。最后,在不同的围手术期时间检测 GPM 患者血清 O6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)启动子的甲基化水平。

结果

筛选出的 burlywood1 组与七氟醚处理的 GBM 组织显著相关。构建了 22 个独立的预后差异基因,构建了 GBM 预后相关基因风险评分,具有良好的预测能力。风险评分与患者年龄密切相关,但与患者性别无关。此外,还分析了高、低风险组对免疫治疗的差异反应,表明七氟醚特征基因在胶质瘤的分类中是一致的。高危患者 T 细胞损伤评分高,对免疫治疗不敏感。最后,在丙泊酚和七氟醚麻醉期间,GBM 患者的 MGMT 启动子甲基化水平降低。

结论

丙泊酚和七氟醚麻醉对 GBM 的基因表达有影响,包括 MGMT 启动子的甲基化水平。基于丙泊酚和七氟醚麻醉的风险评分预后模型具有良好的预后能力,是 GBM 患者的独立预后因素。因此,该模型可作为判断 GBM 患者预后的新生物标志物。

关键信息

基于丙泊酚和七氟醚麻醉的风险评分预后模型具有良好的预后能力,是 GBM 患者的独立预后因素。

基于丙泊酚和七氟醚麻醉的高风险 GBM 患者 T 细胞损伤评分较高,对免疫治疗不敏感。

在 GBM 患者中,丙泊酚和七氟醚麻醉期间血清 MGMT 启动子的甲基化水平降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcb/9979995/d367987a4647/IANN_A_2171109_F0001_C.jpg

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