Proteins with altered levels in plasma from glioblastoma patients as revealed by iTRAQ-based quantitative proteomic analysis

PLoS One. 2012;7(9):e46153. doi: 10.1371/journal.pone.0046153. Epub 2012 Sep 28.

Abstract

Glioblastomas (GBMs) are the most common and lethal primary tumors of the central nervous system with high level of recurrence despite aggressive therapy. Tumor-associated proteins/peptides may appear in the plasma of these patients as a result of disruption of the blood-brain barrier in them, raising the scope for development of plasma-based tests for diagnosis and monitoring the disease. With this objective, we analyzed the levels of proteins present in the plasma from GBM patients using an iTRAQ based LC-MS/MS approach. Analysis with pooled plasma specimens from the patient and healthy control samples revealed high confidence identification of 296 proteins, of which 61 exhibited a fold-change ≥1.5 in the patient group. Forty-eight of them contained signal sequence. A majority have been reported in the differentially expressed transcript or protein profile of GBM tissues; 6 have been previously studied as plasma biomarkers for GBM and 16 for other types of cancers. Altered levels of three representative proteins-ferritin light chain (FTL), S100A9, and carnosinase 1 (CNDP1)-were verified by ELISA in a test set of ten individual plasma specimens. FTL is an inflammation marker also implicated in cancer, S100A9 is an important member of the Ca(2+) signaling cascade reported to be altered in GBM tissue, and CNDP1 has been reported for its role in the regulation of the levels of carnosine, implicated as a potential drug for GBM. These and other proteins in the dataset may form useful starting points for further clinical investigations for the development of plasma-based biomarker panels for GBM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoferritins / blood
  • Apoferritins / genetics*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / blood
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics*
  • Calcium / metabolism
  • Calgranulin B / blood
  • Calgranulin B / genetics*
  • Carnosine / metabolism
  • Chromatography, Liquid
  • Dipeptidases / blood
  • Dipeptidases / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / blood
  • Glioblastoma / diagnosis
  • Glioblastoma / genetics*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / genetics*
  • Proteomics / methods
  • Signal Transduction
  • Tandem Mass Spectrometry

Substances

  • Biomarkers, Tumor
  • Calgranulin B
  • FTL protein, human
  • Neoplasm Proteins
  • Carnosine
  • Apoferritins
  • CNDP1 protein, human
  • Dipeptidases
  • Calcium

Grants and funding

The work reported here was carried out under the Network Project NWP 0004 and IAP 001 supported by the Council of Scientific and Industrial Research (CSIR), Government of India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.