Research Article

Protein profiling of formalin fixed paraffin embedded tissue: Identification of potential biomarkers for pediatric brainstem glioma

  1. Javad Nazarian Dr.1,*,
  2. Mariarita Santi2,
  3. Yetrib Hathout1,†,
  4. Tobey J. MacDonald3,†

Article first published online: 12 JUN 2008

DOI: 10.1002/prca.200780061

Issue

PROTEOMICS - Clinical Applications

PROTEOMICS - Clinical Applications

Special Issue: CARDIOVASCULAR PROTEOMICS

Volume 2, Issue 6, pages 915–924, No. 6 June 2008

Additional Information

How to Cite

Nazarian, J., Santi, M., Hathout, Y. and MacDonald, T. J. (2008), Protein profiling of formalin fixed paraffin embedded tissue: Identification of potential biomarkers for pediatric brainstem glioma. Prot. Clin. Appl., 2: 915–924. doi: 10.1002/prca.200780061

Author Information

  1. 1

    Center for Genetic Medicine Research, Children's National Medical Center, Washington DC, USA

  2. 2

    Pathology, Children's National Medical Center, Washington DC, USA

  3. 3

    Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, Washington DC, USA

  1. †

    These authors contributed equally to the manuscript.

*Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Av. NW, Washington DC, 20010, USA Fax: +1-202-476-6014

Publication History

  1. Issue published online: 12 JUN 2008
  2. Article first published online: 12 JUN 2008
  3. Manuscript Received: 16 SEP 2007

Funded by

  • Isabella Kerr Molina Foundation
  • Children's National Medical Center (CNMC) Mental Retardation Developmental Disabilities Research Center (MRDDRC). Grant Number: P30HD40677

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Keywords:

  • Formalin fixed paraffin embedded;
  • Ingenuity pathway analysis;
  • Pediatric brainstem glioma

Abstract

Little is known about the molecular characteristics of pediatric brainstem gliomas (BSG), which continue to have a dismal prognosis. Targeted molecular strategies are limited due to rarity of biopsy BSG specimen coupled with obstacles associated with the analyses of formalin-fixed paraffin-embedded (FFPE) autopsies. The objective of this study was to develop methodologies to successfully identify the proteome profile from these archived FFPE specimens. Peptides were extracted from both tumor and adjacent normal FFPE brainstem specimen and quantified using 18O proteolytic labeling strategy and LC-MS/MS analysis. The ingenuity pathway analysis software was used to elucidate interactions amongst differentially expressed proteins. We identified 188 proteins of which 54 (29%) were found up-regulated (≥1.5-fold) in BSG compared to normal sections. Of these, 15 (28%) proteins have previously been reported as potential biomarkers for supratentorial malignant gliomas, while the rest appear to be exclusive to pediatric BSG. Because the majority of differentially expressed proteins are unique to BSG, we conclude that pediatric BSG is distinct from supratentorial gliomas. To the best of our knowledge, this is the first proteome profile of pediatric BSG, which may facilitate discovery of novel therapeutic targets for early diagnostics and improving prognostics.

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