Abstract
BackgroundThe mechanisms behind formation and filling of intracranial arachnoid cysts (AC) are poorly understood. The aim of this study was to evaluate AC fluid by proteomics to gain further knowledge about ACs. Two goals were set: 1) Comparison of AC fluid from individual patients to determine whether or not temporal AC is a homogenous condition; and 2) Evaluate the protein content of a pool of AC fluid from several patients and qualitatively compare this with published protein lists of cerebrospinal fluid (CSF) and plasma.MethodsAC fluid from 15 patients with temporal AC was included in this study. In the AC protein comparison experiment, AC fluid from 14 patients was digested, analyzed by LC-MS/MS using a semi-quantitative label-free approach and the data were compared by principal component analysis (PCA) to gain knowledge of protein homogeneity of AC. In the AC proteome evaluation experiment, AC fluid from 11 patients was pooled, digested, and fractionated by SCX chromatography prior to analysis by LC-MS/MS. Proteins identified were compared to published databases of proteins identified from CSF and plasma. AC fluid proteins not found in these two databases were experimentally searched for in lumbar CSF taken from neurologically-normal patients, by a targeted protein identification approach called MIDAS (Multiple Reaction Monitoring (MRM) initiated detection and sequence analysis).ResultsWe did not identify systematic trends or grouping of data in the AC protein comparison experiment, implying low variability between individual proteomic profiles of AC.In the AC proteome evaluation experiment, we identified 199 proteins. When compared to previously published lists of proteins identified from CSF and plasma, 15 of the AC proteins had not been reported in either of these datasets. By a targeted protein identification approach, we identified 11 of these 15 proteins in pooled CSF from neurologically-normal patients, demonstrating that the majority of abundant proteins in AC fluid also can be found in CSF. Compared to plasma, as many as 104 proteins in AC were not found in the list of 3017 plasma proteins.ConclusionsBased on the protein content of AC fluid, our data indicate that temporal AC is a homogenous condition, pointing towards a similar AC filling mechanism for the 14 patients examined. Most of the proteins identified in AC fluid have been identified in CSF, indicating high similarity in the qualitative protein content of AC to CSF, whereas this was not the case between AC and plasma. This indicates that AC is filled with a liquid similar to CSF. As far as we know, this is the first proteomics study that explores the AC fluid proteome.
Highlights
The mechanisms behind formation and filling of intracranial arachnoid cysts (AC) are poorly understood
The lack of systematic trends is an indication of homogenous sample material, suggesting that Arachnoid cysts (AC) is a homogenous condition as evaluated by proteomics
The results of this study indicate that AC fluid is homogenous between patients when evaluated by protein content using a label-free semi-quantitative proteomics approach, a finding supporting results from previous experiments regarding clinical chemistry and mRNA
Summary
The mechanisms behind formation and filling of intracranial arachnoid cysts (AC) are poorly understood. ACs are formed by a splitting of the arachnoid mater (AM) creating a potential space that when filled with fluid appears as a cyst [4,5]. The cyst wall is composed of non-neoplastic arachnoid cells with a capacity to secrete fluid [7,8] that slightly differs in chemical composition from that of cerebrospinal fluid (CSF) [9]. The genetic profile of temporal AC membranes [10] indicates that these cysts represent a homogenous condition, but the underlying cause of AC formation is unknown. Further analyses of the cyst fluid with proteomics, the large-scale studies of proteins, might give indications of the aetiology of AC and shed further light on the mechanisms underlying fluid secretion and transport
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