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胶质母细胞瘤恶性肿瘤全景:胶质母细胞瘤蛋白质组学的荟萃分析以识别改变的生物学途径

The Big Picture of Glioblastoma Malignancy: A Meta-Analysis of Glioblastoma Proteomics to Identify Altered Biological Pathways.

作者信息

Tribe Anna K W, McConnell Melanie J, Teesdale-Spittle Paul H

机构信息

School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand.

出版信息

ACS Omega. 2021 Sep 14;6(38):24535-24544. doi: 10.1021/acsomega.1c02991. eCollection 2021 Sep 28.

DOI:10.1021/acsomega.1c02991
PMID:34604635
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8482494/
Abstract

Glioblastoma is a highly malignant cancer with no effective treatment. It is vital to elucidate the mechanisms which drive glioblastoma in order to identify therapeutic targets. The differences in protein expression between glioblastoma, grade I-III glioma, and normal brain tissue reflect the functional alterations driving malignancy. However, proteomic analysis of glioblastoma has been hampered by the heterogeneity of glioblastoma and the variety of methodology used in its study. To reduce these inconsistencies, we performed a meta-analysis of the literature published since 2015, including 14 datasets from eight papers comparing the whole proteome of glioblastoma to normal brain or grade I-III glioma. We found that 154 proteins were commonly upregulated and 116 proteins were commonly downregulated in glioblastoma compared to normal brain. Meanwhile, 240 proteins were commonly upregulated and 125 proteins were commonly downregulated in glioblastoma compared to grade I-III glioma. Functional enrichment analysis revealed upregulation of proteins involved in mRNA splicing and the immune system and downregulation of proteins involved in synaptic signaling and glucose and glutamine metabolism. The identification of these altered biological pathways provides a basis for deeper investigation in the pursuit of an effective treatment for glioblastoma.

摘要

胶质母细胞瘤是一种高度恶性的癌症,目前尚无有效的治疗方法。阐明驱动胶质母细胞瘤的机制对于确定治疗靶点至关重要。胶质母细胞瘤、I-III级胶质瘤和正常脑组织之间蛋白质表达的差异反映了驱动恶性肿瘤的功能改变。然而,胶质母细胞瘤的蛋白质组学分析受到胶质母细胞瘤的异质性及其研究中使用的多种方法的阻碍。为了减少这些不一致性,我们对2015年以来发表的文献进行了荟萃分析,包括来自八篇论文的14个数据集,这些数据集比较了胶质母细胞瘤与正常脑或I-III级胶质瘤的全蛋白质组。我们发现,与正常脑相比,胶质母细胞瘤中154种蛋白质普遍上调,116种蛋白质普遍下调。同时,与I-III级胶质瘤相比,胶质母细胞瘤中240种蛋白质普遍上调,125种蛋白质普遍下调。功能富集分析显示,参与mRNA剪接和免疫系统的蛋白质上调,而参与突触信号传导以及葡萄糖和谷氨酰胺代谢的蛋白质下调。这些改变的生物途径的鉴定为深入研究寻求胶质母细胞瘤的有效治疗提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ef/8482494/0290e2cb8487/ao1c02991_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ef/8482494/a68ed4d0e1a3/ao1c02991_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ef/8482494/e395e971c338/ao1c02991_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ef/8482494/d5dfc236402b/ao1c02991_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ef/8482494/ede1346f2656/ao1c02991_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ef/8482494/0290e2cb8487/ao1c02991_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ef/8482494/a68ed4d0e1a3/ao1c02991_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ef/8482494/e395e971c338/ao1c02991_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ef/8482494/d5dfc236402b/ao1c02991_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ef/8482494/ede1346f2656/ao1c02991_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ef/8482494/0290e2cb8487/ao1c02991_0006.jpg

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