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Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread
Central nervous system (CNS) tumors are the most common solid tumors in childhood. Since the sensitivity of combined cerebrospinal fluid (CSF) cytology and radiological neuroimaging in detecting meningeal metastases remains relatively low, we sought to characterize the CSF proteome of patients with...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542258/ https://www.ncbi.nlm.nih.gov/pubmed/28526811 http://dx.doi.org/10.18632/oncotarget.17579 |
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author | Spreafico, Filippo Bongarzone, Italia Pizzamiglio, Sara Magni, Ruben Taverna, Elena De Bortoli, Maida Ciniselli, Chiara M. Barzanò, Elena Biassoni, Veronica Luchini, Alessandra Liotta, Lance A. Zhou, Weidong Signore, Michele Verderio, Paolo Massimino, Maura |
author_facet | Spreafico, Filippo Bongarzone, Italia Pizzamiglio, Sara Magni, Ruben Taverna, Elena De Bortoli, Maida Ciniselli, Chiara M. Barzanò, Elena Biassoni, Veronica Luchini, Alessandra Liotta, Lance A. Zhou, Weidong Signore, Michele Verderio, Paolo Massimino, Maura |
author_sort | Spreafico, Filippo |
collection | PubMed |
description | Central nervous system (CNS) tumors are the most common solid tumors in childhood. Since the sensitivity of combined cerebrospinal fluid (CSF) cytology and radiological neuroimaging in detecting meningeal metastases remains relatively low, we sought to characterize the CSF proteome of patients with CSF tumors to identify biomarkers predictive of metastatic spread. CSF samples from 27 children with brain tumors and 13 controls (extra-CNS non-Hodgkin lymphoma) were processed using core-shell hydrogel nanoparticles, and analyzed with reverse-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS). Candidate proteins were identified with Fisher's exact test and/or a univariate logistic regression model. Reverse phase protein array (RPPA), Western blot (WB), and ELISA were used in the training set and in an independent set of CFS samples (60 cases, 14 controls) to validate our discovery findings. Among the 558 non-redundant proteins identified by LC-MS/MS, 147 were missing from the CSF database at http://www.biosino.org. Fourteen of the 26 final top-candidate proteins were chosen for validation with WB, RPPA and ELISA methods. Six proteins (type 1 collagen, insulin-like growth factor binding protein 4, procollagen C-endopeptidase enhancer 1, glial cell-line derived neurotrophic factor receptor α2, inter-alpha-trypsin inhibitor heavy chain 4, neural proliferation and differentiation control protein-1) revealed the ability to discriminate metastatic cases from controls. Combining a unique dataset of CSFs from pediatric CNS tumors with a novel enabling nanotechnology led us to identify CSF proteins potentially related to metastatic status. |
format | Online Article Text |
id | pubmed-5542258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-55422582017-08-07 Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread Spreafico, Filippo Bongarzone, Italia Pizzamiglio, Sara Magni, Ruben Taverna, Elena De Bortoli, Maida Ciniselli, Chiara M. Barzanò, Elena Biassoni, Veronica Luchini, Alessandra Liotta, Lance A. Zhou, Weidong Signore, Michele Verderio, Paolo Massimino, Maura Oncotarget Research Paper Central nervous system (CNS) tumors are the most common solid tumors in childhood. Since the sensitivity of combined cerebrospinal fluid (CSF) cytology and radiological neuroimaging in detecting meningeal metastases remains relatively low, we sought to characterize the CSF proteome of patients with CSF tumors to identify biomarkers predictive of metastatic spread. CSF samples from 27 children with brain tumors and 13 controls (extra-CNS non-Hodgkin lymphoma) were processed using core-shell hydrogel nanoparticles, and analyzed with reverse-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS). Candidate proteins were identified with Fisher's exact test and/or a univariate logistic regression model. Reverse phase protein array (RPPA), Western blot (WB), and ELISA were used in the training set and in an independent set of CFS samples (60 cases, 14 controls) to validate our discovery findings. Among the 558 non-redundant proteins identified by LC-MS/MS, 147 were missing from the CSF database at http://www.biosino.org. Fourteen of the 26 final top-candidate proteins were chosen for validation with WB, RPPA and ELISA methods. Six proteins (type 1 collagen, insulin-like growth factor binding protein 4, procollagen C-endopeptidase enhancer 1, glial cell-line derived neurotrophic factor receptor α2, inter-alpha-trypsin inhibitor heavy chain 4, neural proliferation and differentiation control protein-1) revealed the ability to discriminate metastatic cases from controls. Combining a unique dataset of CSFs from pediatric CNS tumors with a novel enabling nanotechnology led us to identify CSF proteins potentially related to metastatic status. Impact Journals LLC 2017-05-03 /pmc/articles/PMC5542258/ /pubmed/28526811 http://dx.doi.org/10.18632/oncotarget.17579 Text en Copyright: © 2017 Spreafico et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Spreafico, Filippo Bongarzone, Italia Pizzamiglio, Sara Magni, Ruben Taverna, Elena De Bortoli, Maida Ciniselli, Chiara M. Barzanò, Elena Biassoni, Veronica Luchini, Alessandra Liotta, Lance A. Zhou, Weidong Signore, Michele Verderio, Paolo Massimino, Maura Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread |
title | Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread |
title_full | Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread |
title_fullStr | Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread |
title_full_unstemmed | Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread |
title_short | Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread |
title_sort | proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542258/ https://www.ncbi.nlm.nih.gov/pubmed/28526811 http://dx.doi.org/10.18632/oncotarget.17579 |
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