Construction and validation of a risk model based on the key SNARE proteins to predict the prognosis and immune microenvironment of gliomas

Author:

Yin Luxin,Xu Yiqiang,Yin Jiale,Cheng Hai,Xiao Weihan,Wu Yue,Ji Daofei,Gao Shangfeng

Abstract

BackgroundSynaptic transmission between neurons and glioma cells can promote glioma progression. The soluble N-ethylmaleimide-sensitive fusion factor attachment protein receptors (SNARE) play a key role in synaptic functions. We aimed to construct and validate a novel model based on the SNARE proteins to predict the prognosis and immune microenvironment of glioma.MethodsDifferential expression analysis and COX regression analysis were used to identify key SRGs in glioma datasets, and we constructed a prognostic risk model based on the key SRGs. The prognostic value and predictive performance of the model were assessed in The Cancer Genome Atlas (TCGA) and Chinese glioma Genome Atlas (CGGA) datasets. Functional enrichment analysis and immune-related evaluation were employed to reveal the association of risk scores with tumor progression and microenvironment. A prognostic nomogram containing the risk score was established and assessed by calibration curves and time-dependent receiver operating characteristic curves. We verified the changes of the key SRGs in glioma specimens and cells by real-time quantitative PCR and Western blot analyses.ResultsVesicle-associated membrane protein 2 (VAMP2) and vesicle-associated membrane protein 5 (VAMP5) were identified as two SRGs affecting the prognoses of glioma patients. High-risk patients characterized by higher VAMP5 and lower VAMP2 expression had a worse prognosis. Higher risk scores were associated with older age, higher tumor grades, IDH wild-type, and 1p19q non-codeletion. The SRGs risk model showed an excellent predictive performance in predicting the prognosis in TCGA and CGGA datasets. Differentially expressed genes between low- and high-risk groups were mainly enriched in the pathways related to immune infiltration, tumor metastasis, and neuronal activity. Immune score, stromal score, estimate score, tumor mutational burden, and expression of checkpoint genes were positively correlated with risk scores. The nomogram containing the risk score showed good performance in predicting the prognosis of glioma. Low VAMP2 and high VAMP5 were found in different grades of glioma specimens and cell lines.ConclusionWe constructed and validated a novel risk model based on the expression of VAMP2 and VAMP5 by bioinformatics analysis and experimental confirmation. This model might be helpful for clinically predicting the prognosis and response to immunotherapy of glioma patients.

Publisher

Frontiers Media SA

Subject

Cellular and Molecular Neuroscience,Molecular Biology

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3