Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread

F. Spreafico, I. Bongarzone, S. Pizzamiglio, R. Magni, E. Taverna, M. De Bortoli, C.M. Ciniselli, E. Barzanò, V. Biassoni, A. Luchini, L.A. Liotta, W. Zhou, M. Signore, P. Verderio, M. Massimino

Research output: Contribution to journalArticlepeer-review

Abstract

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. © Spreafico et al.
Original languageEnglish
Pages (from-to)46177-46190
Number of pages14
JournalOncotarget
Volume8
Issue number28
Publication statusPublished - 2017

Keywords

  • Cerebrospinal fluid
  • Liquid chromatography/electrospray tandem mass spectrometry
  • Pediatric central nervous system tumors
  • Protein-based biomarker
  • Proteomic analysis
  • collagen type 1
  • core shell hydrogel nanoparticle
  • glial cell line derived neurotrophic factor receptor
  • glial cell line derived neurotrophic factor receptor alpha2
  • inter alpha trypsin inhibitor
  • inter alpha trypsin inhibitor heavy chain 4
  • membrane protein
  • nanoparticle
  • neural proliferation and differentiation control protein 1
  • procollagen C endopeptidase enhancer 1
  • proteome
  • somatomedin binding protein 4
  • unclassified drug
  • adolescent
  • adult
  • Article
  • case control study
  • central nervous system cancer
  • cerebrospinal fluid analysis
  • child
  • controlled study
  • disease association
  • enzyme linked immunosorbent assay
  • female
  • human
  • liquid chromatography-mass spectrometry
  • major clinical study
  • male
  • metastasis
  • nanotechnology
  • nonhodgkin lymphoma
  • prospective study
  • protein analysis
  • protein microarray
  • proteomics
  • reverse phase protein array
  • reversed phase liquid chromatography
  • Western blotting

Fingerprint Dive into the research topics of 'Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread'. Together they form a unique fingerprint.

Cite this