부산대학교 도서관

Simple Summary: Cystic brain tumors are a heterogeneous category comprising a wide range of lesions both intra- and extracerebral. While the presence of large cysts is hallmark of rare benign tumors, such as craniopharingiomas, hemangioblastomas and secretory meningiomas, cysts may less frequently develop into 8th nerve schwannomas and high-grade gliomas. The mechanisms leading to cyst formation have not been clarified. The most commonly accepted hypothesis indicates an increased vascular permeability with serum protein accumulation as the possible culprit. In order to clarify the composition of cystic fluid and its possible variations in different tumors, we performed an untargeted proteomic analysis of cystic fluid serially sampled by mini-invasive methods from secretory meningioma (SM), cystic schwannoma (CS) and cystic high-grade glioma (CG). Our data indicate that proteins contained in the cystic fluid of those tumors remains stable over time. Together with proteins originating from serum and cerebrospinal fluid (CSF) that were common to all cystic fluids examined, we identified proteins whose presence was restricted to specific tumors. Furthermore, applying a protein–protein interactions network analysis and an overrepresentation evaluation, we were able to identify functional pathways that were typical for each of the three tumor histotypes we studied. Our results demonstrate that the cystic fluid sampled from different tumors contains proteins derived from multiple sources: serum, CSF and the tumor itself, indicating that the proteomic study of this tumor component, which is often neglected, may help us to clarify tumor–host tissue interactions with potential diagnostic and therapeutic implications. Cystic formation in human primary brain tumors is a relatively rare event whose incidence varies widely according to the histotype of the tumor. Composition of the cystic fluid has mostly been characterized in samples collected at the time of tumor resection and no indications of the evolution of cystic content are available. We characterized the evolution of the proteome of cystic fluid using a bottom-up proteomic approach on sequential samples obtained from secretory meningioma (SM), cystic schwannoma (CS) and cystic high-grade glioma (CG). We identified 1008 different proteins; 74 of these proteins were found at least once in the cystic fluid of all tumors. The most abundant proteins common to all tumors studied derived from plasma, with the exception of prostaglandin D2 synthase, which is a marker of cerebrospinal fluid origin. Overall, the protein composition of cystic fluid obtained at different times from the same tumor remained stable. After the identification of differentially expressed proteins (DEPs) and the protein–protein interaction network analysis, we identified the presence of tumor-specific pathways that may help to characterize tumor–host interactions. Our results suggest that plasma proteins leaking from local blood–brain barrier disruption are important contributors to cyst fluid formation, but cerebrospinal fluid (CSF) and the tumor itself also contribute to the cystic fluid proteome and, in some cases, as with immunoglobulin G, shows tumor-specific variations that cannot be simply explained by differences in vessel permeability or blood contamination. [ABSTRACT FROM AUTHOR]