尽管近年来我们对驱动基因突变和脑肿瘤内异质性的认识有了新的进展，无论是原发性还是转移性（也称为继发性）脑肿瘤，在蛋白质组变化方面我们的理解仍然不足。本研究旨在为脑肿瘤研究提供信息源，并基于蛋白质组学分析区分原发性脑肿瘤和继发性脑肿瘤的头颅外起源。 我们按照以下方式组织了最常见的脑肿瘤：WHO二至四级的胶质瘤，带有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，采用无标签定量质谱蛋白质组学方法。 总共鉴定了8165个蛋白质组，其中4383个蛋白质在下游分析中以50%的有效强度值进行了筛选。对BrMs的蛋白质组学分析揭示了多个起源间共享的保守特征。虽然发现了用于区分不同级别胶质瘤以及IDH1突变和野生型胶质瘤的蛋白质组学异质性。此外，BrMs和胶质瘤之间在信号通路水平上也存在明显的差异。具体而言，BrMs在侵袭大脑后展示了突出的增殖和免疫调节信号通路，而胶质瘤主要参与了侵袭过程。 我们对BrMs和胶质瘤的广泛蛋白质组进行了特征化。这些发现对于发展针对BrMs和胶质瘤的靶向治疗具有巨大的潜力。 © 2023 Wiley-VCH GmbH.

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.© 2023 Wiley-VCH GmbH.