Abstract
Ependymoma pediatric brain tumor occurs at approximate frequencies of 10–15% in supratentorial and 20–30% in posterior fossa regions. These tumors have an almost selective response to surgery and relative and confirmed resistance to radiotherapy and chemotherapic agents, respectively. Alongside histopathological grading, clinical and treatment evaluation of ependymomas currently consider the tumor localization and the genomic outlined associated molecular subgroups, with the supratentorial and the posterior fossa ependymomas nowadays considered diverse diseases. On these grounds and in trying to better understand the molecular features of these tumors, the present investigation aimed to originally investigate the proteomic profile of pediatric ependymoma tissues of different grade and localization by mass spectrometry platforms to disclose potential distinct protein phenotypes. To this purpose, acid-soluble and acid-insoluble fractions of ependymoma tumor tissues homogenates were analyzed by LC-MS following both the top-down and the shotgun proteomic approaches, respectively, to either investigate the intact proteome or its digested form. The two approaches were complementary in profiling the ependymoma tumor tissues and showed distinguished profiles for supratentorial and posterior fossa ependymomas and for WHO II and III tumor grades. Top-down proteomic analysis revealed statistically significant higher levels of thymosin beta 4, 10 kDa heat shock protein, non-histone chromosomal protein HMG-17, and mono-/uncitrullinated forms ratio of the glial fibrillary acidic protein (GFAP) fragment 388–432 in supratentorial ependymomas—the same GFAP fragment as well as the hemoglobin alpha- and the beta-chain marked grade II with respect to grade III posterior fossa ependymomas. Gene ontology classification of shotgun data of the identified cancer and the non-cancer related proteins disclosed protein elements exclusively marking tumor localization and pathways that were selectively overrepresented. These results, although preliminary, seem consistent with different protein profiles of ependymomas of diverse grade of aggressiveness and brain region development and contributed to enlarging the molecular knowledge of this still enigmatic tumor.
Highlights
Ependymomas are rare malignances and represent about 10% of all pediatric CNS tumors [1]
After ependymoma (EP) tissue homogenization, the resulting acid-soluble fraction was processed by LC-MS analysis following the top-down proteomics approach, while the acid insoluble pellet was analyzed by the shotgun strategy
The present investigation represents, to the best of our knowledge, the first protein fingerprinting of ependymoma tissue obtained by the application of a top-down/bottom-up integrated proteomic platform, revealing the first hallmark of its intact proteome, post-translational modifications (PTMs) and naturally occurring bioactive peptidome, and the first preliminary proteomic study extended to ependymoma tissue of different grade and localization
Summary
Ependymomas are rare malignances and represent about 10% of all pediatric CNS tumors [1] More in detail, they account for approximately 10–15% of supratentorial and 20–30% of posterior fossa tumors in children. The extent of surgical resection remains the main prognostic factor; a gross total surgical resection is hardly achievable (50–60% of cases) [2]. This occurs especially in the molecular subgroup A, where the tumor affects young children and typically extends to the cerebello-pontine angle with subsequent encasement of the cranial nerves and the arterial branches of the posterior Willis’ circle [5,6]. A significant proportion of children with totally resected posterior fossa ependymomas experience a tumor recurrence [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
