Magrassi Lorenzo, Brambilla Francesca, Viganò Raffaello, Di Silvestre Dario, Benazzi Louise, Bellantoni Giuseppe, Danesino Gian Marco, Comincini Sergio, Mauri Pierluigi
Neurosurgery, Dipartimento di Scienze Clinico-Chirurgiche e Pediatriche, Università degli Studi di Pavia, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, Italy.
Istituto di Genetica Molecolare-CNR, 27100 Pavia, Italy.
Cancers (Basel). 2023 Aug 11;15(16):4070. doi: 10.3390/cancers15164070.
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.
人类原发性脑肿瘤中的囊性形成是一种相对罕见的现象，其发生率根据肿瘤的组织学类型有很大差异。囊性液体的成分大多是在肿瘤切除时采集的样本中得以表征的，目前尚无关于囊性内容物演变的相关迹象。我们采用自下而上的蛋白质组学方法，对从分泌性脑膜瘤（SM）、囊性神经鞘瘤（CS）和囊性高级别胶质瘤（CG）获取的连续样本中的囊性液体蛋白质组演变进行了表征。我们鉴定出了1008种不同的蛋白质；其中74种蛋白质在所有肿瘤的囊性液体中至少被发现过一次。除了作为脑脊液来源标志物的前列腺素D2合成酶外，所有研究肿瘤共有的最丰富蛋白质均来源于血浆。总体而言，从同一肿瘤在不同时间获取的囊性液体的蛋白质组成保持稳定。在鉴定出差异表达蛋白（DEP）并进行蛋白质 - 蛋白质相互作用网络分析后，我们确定了可能有助于表征肿瘤 - 宿主相互作用的肿瘤特异性途径。我们的结果表明，从局部血脑屏障破坏处渗漏的血浆蛋白是囊液形成的重要因素，但脑脊液（CSF）和肿瘤本身也对囊性液体蛋白质组有贡献，并且在某些情况下，如免疫球蛋白G，显示出肿瘤特异性变化，这不能简单地用血管通透性差异或血液污染来解释。
