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多组学数据分析与免疫相关预后特征的鉴定及其对胶质母细胞瘤预后和免疫检查点阻断治疗的潜在影响

Multiomics Data Analysis and Identification of Immune-Related Prognostic Signatures With Potential Implications in Prognosis and Immune Checkpoint Blockade Therapy of Glioblastoma.

作者信息

Ma Shuai, Wang Fang, Wang Nan, Jin Jiaqi, Ba Yixu, Ji Hang, Du Jianyang, Hu Shaoshan

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital Affiliated to Hangzhou Medical College, Hangzhou, China.

出版信息

Front Neurol. 2022 May 20;13:886913. doi: 10.3389/fneur.2022.886913. eCollection 2022.

Abstract

BACKGROUND

In recent years, glioblastoma multiforme (GBM) has been a concern of many researchers, as it is one of the main drivers of cancer-related deaths worldwide. GBM in general usually does not responding well to immunotherapy due to its unique microenvironment.

METHODS

To uncover any further informative immune-related prognostic signatures, we explored the immune-related distinction in the genetic or epigenetic features of the three types (expression profile, somatic mutation, and DNA methylation). Twenty eight immune-related hub genes were identified by Weighted Gene Co-Expression Network Analysis (WGCNA). The findings showed that three genes (, and ) were identified to construct an immune-related prognostic model (IRPM) by lasso regression. Then, we used three hub genes to construct an IRPM for GBM and clarify the immunity, mutation, and methylation characteristics.

RESULTS

Survival analysis of patients undergoing anti-program cell death protein 1 (anti-PD-1) therapy showed that overall survival was superior in the low-risk group than in the high-risk group. The high-risk group had an association with epithelial-mesenchymal transition (EMT), high immune cell infiltration, immune activation, a low mutation number, and high methylation, while the low-risk group was adverse status.

CONCLUSIONS

In conclusion, IRPM is a promising tool to distinguish the prognosis of patients and molecular and immune characteristics in GBM, and the IRPM risk score can be used to predict patient sensitivity to checkpoint inhibitor blockade therapy. Thus, three immune-related signatures will guide us in improving treatment strategies and developing objective diagnostic tools.

摘要

背景

近年来,多形性胶质母细胞瘤(GBM)一直是众多研究人员关注的焦点,因为它是全球癌症相关死亡的主要驱动因素之一。由于其独特的微环境,GBM 总体上通常对免疫疗法反应不佳。

方法

为了发现更多有信息价值的免疫相关预后特征,我们探索了三种类型(表达谱、体细胞突变和 DNA 甲基化)在遗传或表观遗传特征方面的免疫相关差异。通过加权基因共表达网络分析(WGCNA)鉴定了 28 个免疫相关枢纽基因。研究结果表明,通过套索回归鉴定出三个基因(、和)来构建免疫相关预后模型(IRPM)。然后,我们使用三个枢纽基因构建 GBM 的 IRPM,并阐明其免疫、突变和甲基化特征。

结果

接受抗程序性细胞死亡蛋白 1(抗 PD - 1)治疗患者的生存分析表明,低风险组的总生存期优于高风险组。高风险组与上皮 - 间质转化(EMT)、高免疫细胞浸润、免疫激活、低突变数和高甲基化相关,而低风险组则处于不利状态。

结论

总之,IRPM 是一种有前景的工具,可用于区分 GBM 患者的预后以及分子和免疫特征,并且 IRPM 风险评分可用于预测患者对检查点抑制剂阻断疗法的敏感性。因此,三个免疫相关特征将指导我们改进治疗策略并开发客观的诊断工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba7b/9165649/45ae1bf88663/fneur-13-886913-g0001.jpg

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