{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T10:59:00Z","timestamp":1769857140167,"version":"3.49.0"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Ependymoma pediatric brain tumor occurs at approximate frequencies of 10\u201315% in supratentorial and 20\u201330% 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\u2013432 in supratentorial ependymomas\u2014the 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.<\/jats:p>","DOI":"10.3390\/cancers12030674","type":"journal-article","created":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T03:54:14Z","timestamp":1584590054000},"page":"674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ependymoma Pediatric Brain Tumor Protein Fingerprinting by Integrated Mass Spectrometry Platforms: A Pilot Investigation"],"prefix":"10.3390","volume":"12","author":[{"given":"Diana Valeria","family":"Rossetti","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze biotecnologiche di base, cliniche intensivologiche e perioperatorie, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Massimi","sequence":"additional","affiliation":[{"name":"UOC Neurochirurgia Infantile, Dipartimento di scienze dell\u2019invecchiamento, neurologiche, ortopediche e della testa-collo, Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Martelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze biotecnologiche di base, cliniche intensivologiche e perioperatorie, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0124-2234","authenticated-orcid":false,"given":"Federica","family":"Vincenzoni","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze biotecnologiche di base, cliniche intensivologiche e perioperatorie, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Di Silvestre","sequence":"additional","affiliation":[{"name":"UOC Neurochirurgia Infantile, Dipartimento di scienze dell\u2019invecchiamento, neurologiche, ortopediche e della testa-collo, Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Scorpio","sequence":"additional","affiliation":[{"name":"UOC Neurochirurgia Infantile, Dipartimento di scienze dell\u2019invecchiamento, neurologiche, ortopediche e della testa-collo, Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianpiero","family":"Tamburrini","sequence":"additional","affiliation":[{"name":"UOC Neurochirurgia Infantile, Dipartimento di scienze dell\u2019invecchiamento, neurologiche, ortopediche e della testa-collo, Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Caldarelli","sequence":"additional","affiliation":[{"name":"UOC Neurochirurgia Infantile, Dipartimento di scienze dell\u2019invecchiamento, neurologiche, ortopediche e della testa-collo, Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Urbani","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze biotecnologiche di base, cliniche intensivologiche e perioperatorie, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"},{"name":"UOC Chimica, Biochimica e Biologia Molecolare Clinica, Fondazione Policlinico Universitario Agostino Gemelli\u2014IRCCS, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Desiderio","sequence":"additional","affiliation":[{"name":"Istituto di Scienze e Tecnologie Chimiche \u201cGiulio Natta\u201d, Consiglio Nazionale delle Ricerche, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1007\/s12094-019-02082-2","article-title":"Central nervous system ependymoma: Clinical implications of the new molecular classification, treatment guidelines and controversial issues","volume":"21","year":"2019","journal-title":"Clin. Transl. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1007\/s00381-009-0874-y","article-title":"Survival following treatment for intracranial ependymoma: A review","volume":"25","author":"Tamburrini","year":"2009","journal-title":"Childs Nerv. Syst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00401-016-1643-0","article-title":"The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants","volume":"133","author":"Pajtler","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"246","DOI":"10.3171\/2011.6.PEDS1142","article-title":"Second-look surgery for ependymoma: The Italian experience","volume":"8","author":"Massimino","year":"2011","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ccr.2011.07.007","article-title":"Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma","volume":"20","author":"Witt","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature13108","article-title":"Epigenomic alterations define lethal CIMP-positive ependymomas of infancy","volume":"506","author":"Mack","year":"2014","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2217\/14796694.5.2.207","article-title":"Intracranial ependymoma: Factors affecting outcome","volume":"5","author":"Massimino","year":"2009","journal-title":"Future Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1586\/14789450.2014.939633","article-title":"The proteomics of pediatric brain tumors","volume":"11","author":"Anagnostopoulos","year":"2014","journal-title":"Expert. Rev. Proteom."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1097\/01.jnen.0000240475.35414.c3","article-title":"Identification of novel biomarkers in pediatric primitive neuroectodermal tumors and ependymomas by proteome-wide analysis","volume":"66","author":"Kros","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/neuonc\/not308","article-title":"Pre-B-cell leukemia homeobox interacting protein 1 is overexpressed in astrocytoma and promotes tumor cell growth and migration","volume":"16","author":"Aronica","year":"2014","journal-title":"Neuro Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"127","DOI":"10.21873\/cgp.20025","article-title":"Pediatric Ependymoma: A Proteomics Perspective","volume":"14","author":"Tsangaris","year":"2017","journal-title":"Cancer Genom. Proteom."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.dib.2017.10.001","article-title":"The Pediatric Ependymoma Protein Database (PEPD)","volume":"15","author":"Tsangaris","year":"2017","journal-title":"Data Brief."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1093\/neuonc\/noz058","article-title":"EZHIP\/CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma","volume":"21","author":"Papageorgiou","year":"2019","journal-title":"Neuro Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1177\/1066896918800812","article-title":"L1CAM Immunopositivity in Anaplastic Supratentorial Ependymomas: Correlation with Clinical and Histological Parameters","volume":"27","author":"Chavali","year":"2019","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1007\/s12094-018-1876-6","article-title":"Prognostic and microRNA profile analysis for CD44 positive expression pediatric posterior fossa ependymoma","volume":"20","author":"Shu","year":"2018","journal-title":"Clin. Transl. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105488","DOI":"10.1016\/j.clineuro.2019.105488","article-title":"Pediatric ependymoma: GNAO1, ASAH1, IMMT and IPO7 protein expression and 5-year prognosis correlation","volume":"186","year":"2019","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1080\/10409238.2018.1447543","article-title":"Cryptides: Latent peptides everywhere","volume":"53","author":"Iavarone","year":"2018","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s00381-013-2069-9","article-title":"Identification of Thymosins beta4 and beta10 in paediatric craniopharyngioma cystic fluid","volume":"29","author":"Desiderio","year":"2013","journal-title":"Childs Nerv. Syst."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1039\/C5MB00076A","article-title":"Integrated proteomic platforms for the comparative characterization of medulloblastoma and pilocytic astrocytoma pediatric brain tumors: A preliminary study","volume":"11","author":"Martelli","year":"2015","journal-title":"Mol. Biosyst."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1007\/s00381-010-1245-4","article-title":"The role of inflammation in the genesis of the cystic component of craniopharyngiomas","volume":"26","author":"Pettorini","year":"2010","journal-title":"Childs Nerv. Syst."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1002\/elps.201300578","article-title":"Proteomic Characterization of pediatric craniopharyngioma intracystic fluid by LC-MS top-down\/bottom-up integrated approaches","volume":"35","author":"Martelli","year":"2014","journal-title":"Electrophoresis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1002\/pmic.201400313","article-title":"ProSight lite: Graphical software to analyze top-down mass spectrometry data","volume":"15","author":"Fellers","year":"2015","journal-title":"Proteomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4594","DOI":"10.1021\/pr500806k","article-title":"Proteomic study of pilocytic astrocytoma pediatric brain tumorintracystic fluid","volume":"13","author":"Inserra","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6129437","DOI":"10.1155\/2016\/6129437","article-title":"C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function","volume":"2016","author":"Blaurock","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3961","DOI":"10.1021\/acs.jproteome.6b00392","article-title":"Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 2.1","volume":"15","author":"Deutsch","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s10014-019-00338-x","article-title":"Review of ependymomas: Assessment of consensus in pathological diagnosis and correlations with genetic profiles and outcome","volume":"36","author":"Sasaki","year":"2019","journal-title":"Brain Tumor Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e995033","DOI":"10.4161\/23723556.2014.995033","article-title":"ERBB2 oncogenicity: ERBIN helps to perform the job","volume":"2","author":"Mei","year":"2015","journal-title":"Mol. Cell. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4839","DOI":"10.1158\/0008-5472.CAN-17-3629","article-title":"Erbin Suppresses KSR1-Mediated RAS\/RAF Signaling and Tumorigenesis in Colorectal Cancer","volume":"78","author":"Stevens","year":"2018","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0083-6729(03)01007-0","article-title":"The thymosins. Prothymosin alpha, parathymosin, and beta-thymosins: Structure and function","volume":"66","author":"Hannappel","year":"2003","journal-title":"Vitam Horm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.17219\/acem\/32026","article-title":"Thymosin \u03b2 as an Actin-binding Protein with a Variety of Functions","volume":"25","author":"Kuzan","year":"2016","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s00268-004-7817-2","article-title":"Roles of thymosins in cancers and other organ systems","volume":"29","author":"Chen","year":"2005","journal-title":"World J. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1023\/A:1007677003387","article-title":"Glial fibrillary acidic protein: GFAP-thirty-one years (1969\u20132000)","volume":"25","author":"Eng","year":"2000","journal-title":"Neurochem. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1007\/s00018-011-0735-1","article-title":"Vimentin in cancer and its potential as a molecular target for cancer therapy","volume":"68","author":"Satelli","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/jnr.20431","article-title":"Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer\u2019s disease","volume":"80","author":"Ishigami","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"426","DOI":"10.14348\/molcells.2014.2359","article-title":"Vimentin is involved in peptidylarginine deiminase 2-induced apoptosis of activated Jurkat cells","volume":"37","author":"Hsu","year":"2014","journal-title":"Mol. Cells"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1016\/j.biocel.2006.03.008","article-title":"Citrullination: A posttranslational modification in health and disease","volume":"38","author":"Tarcsa","year":"2006","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1158\/0008-5472.CAN-18-2797","article-title":"Citrullination in Cancer","volume":"79","author":"Yuzhalin","year":"2019","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.tibs.2014.02.004","article-title":"Serine and glycine metabolism in cancer","volume":"39","author":"Amelio","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_40","first-page":"53","article-title":"Opioid therapy and tumor progression","volume":"8","author":"Mousa","year":"2009","journal-title":"Adv. Palliat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1002\/pmic.201100499","article-title":"Cerebrospinal fluid top-down proteomics evidenced the potential biomarker role of LVV- and VV-hemorphin-7 in posterior cranial fossa pediatric brain tumors","volume":"12","author":"Desiderio","year":"2012","journal-title":"Proteomics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fcell.2017.00043","article-title":"Metabolic Reprogramming in Glioma","volume":"5","author":"Strickland","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1055\/s-0035-1566120","article-title":"Hemoglobins, Hemorphins, and 11p15.5 Chromosomal Region in Cancer Biology and \u0130mmunity with Special Emphasis for Brain Tumors","volume":"77","author":"Altinoz","year":"2016","journal-title":"J. Neurol. Surg. A Cent. Eur. Neurosurg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1074\/mcp.M700487-MCP200","article-title":"Protein Profiling of Human Breast Tumor Cells Identifies Novel Biomarkers Associated with Molecular Subtypes","volume":"7","author":"Bertucci","year":"2008","journal-title":"Mol. Cell. Proteom."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1038\/sj.bjc.6602634","article-title":"Decreased expression of haemoglobin beta (HBB) gene in anaplastic thyroid cancer and recovery of its expression inhibits cell growth","volume":"92","author":"Onda","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"D183","DOI":"10.1093\/nar\/gkw1138","article-title":"PANTHER version 11: Expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements","volume":"45","author":"Mi","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/pro.3711","article-title":"KEGG Mapper for inferring cellular functions from protein sequences","volume":"29","author":"Kanehisa","year":"2020","journal-title":"Protein Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D362","DOI":"10.1093\/nar\/gkw937","article-title":"The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible","volume":"45","author":"Szklarczyk","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Fagerberg","year":"2015","journal-title":"Science"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/3\/674\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:06:44Z","timestamp":1760173604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/3\/674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,13]]},"references-count":49,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["cancers12030674"],"URL":"https:\/\/doi.org\/10.3390\/cancers12030674","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,13]]}}}