Institutes of Biomedical Sciences, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
Department of Neurosurgery, School of Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China.
Proteomics Clin Appl. 2024 Mar;18(2):e2300010. doi: 10.1002/prca.202300010. Epub 2023 Sep 19.
Despite recent advancements in our understanding of driver gene mutations and heterogeneity within brain tumors, whether primary or metastatic (also known as secondary), our comprehension of proteomic changes remains inadequate. The aim of this study is to provide an informative source for brain tumor researches, and distinguish primary brain tumors and secondary brain tumors from extracranial origins based on proteomic analysis.
We assembled the most frequent brain tumors as follows: gliomas from WHO grade 2 to 4, with IDH1 mutations and wildtypes; brain metastases (BrMs) originating from lung cancer (LC), breast cancer (BC), ovarian cancer (OC), and colorectal cancer (CC). A total of 29 tissue samples were analyzed by label free quantitative mass spectrometry-based proteomics.
In total, 8165 protein groups were quantified, of which 4383 proteins were filtered at 50% valid intensity values for downstream analysis. Proteomic analysis of BrMs reveals conserved features shared among multiple origins. While proteomic heterogeneities were found for discriminating different grades of gliomas, as well as IDH1 mutant and wildtype gliomas. In addition, notable distinctions were observed at the pathway level between BrMs and gliomas. Specifically, BrMs exhibited characteristic pathways focused on proliferation and immunomodulation after colonizing the brain, whereas gliomas primarily engaged in invasion processes.
We characterized an extensive proteomic landscape of BrMs and gliomas. These findings have promising implications for the development of targeted therapies for BrMs and gliomas.
尽管我们最近对脑肿瘤中的驱动基因突变和异质性有了更多的了解，无论是原发性还是转移性（也称为继发性），但我们对蛋白质组变化的理解仍然不够。本研究的目的是为脑肿瘤研究提供一个信息来源，并基于蛋白质组分析区分原发性脑肿瘤和来自颅外起源的继发性脑肿瘤。
我们将最常见的脑肿瘤组装如下：从 2 级到 4 级的星形细胞瘤，有 IDH1 突变和野生型；来自肺癌（LC）、乳腺癌（BC）、卵巢癌（OC）和结直肠癌（CC）的脑转移瘤（BrMs）。共分析了 29 个组织样本的无标记定量质谱蛋白质组学。
总共定量了 8165 个蛋白质组，其中 4383 个蛋白质在 50%有效强度值下被过滤用于下游分析。BrMs 的蛋白质组分析揭示了多个起源之间共享的保守特征。虽然在区分不同等级的星形细胞瘤以及 IDH1 突变型和野生型星形细胞瘤时发现了蛋白质组异质性，但在不同等级的星形细胞瘤之间也存在显著差异。此外，在 BrMs 和星形细胞瘤之间的途径水平上也观察到了显著的差异。具体来说，BrMs 在定植大脑后表现出以增殖和免疫调节为特征的特征性途径，而星形细胞瘤主要参与入侵过程。
我们描绘了 BrMs 和星形细胞瘤的广泛蛋白质组景观。这些发现为 BrMs 和星形细胞瘤的靶向治疗的发展提供了有前景的启示。
