title: Proteins with altered levels in plasma from glioblastoma patients as revealed by iTRAQ-based quantitative proteomic analysis.
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.
authors.affiliation: Centre for Cellular and Molecular Biology (CSIR), Hyderabad, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Gautam
authors.forename: Sudha C
authors.initials: SC
authors.lastname: Nair
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Gupta
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sharma
authors.forename: Ravindra Varma
authors.initials: RV
authors.lastname: Polisetty
authors.forename: Megha S
authors.initials: MS
authors.lastname: Uppin
authors.forename: Challa
authors.initials: C
authors.lastname: Sundaram
authors.forename: Aneel K
authors.initials: AK
authors.lastname: Puligopu
authors.forename: Praveen
authors.initials: P
authors.lastname: Ankathi
authors.forename: Aniruddh K
authors.initials: AK
authors.lastname: Purohit
authors.forename: Giriraj R
authors.initials: GR
authors.lastname: Chandak
authors.forename: H C
authors.initials: HC
authors.lastname: Harsha
authors.forename: Ravi
authors.initials: R
authors.lastname: Sirdeshmukh
mesh_terms: D001052:Apoferritins / Q000097:blood / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001932:Brain Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D040502:Calgranulin B / Q000097:blood / Q000235:genetics*; D002336:Carnosine / Q000378:metabolism; D002853:Chromatography, Liquid; D004150:Dipeptidases / Q000097:blood / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics*; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D040502:Calgranulin B; C507433:FTL protein, human; D009363:Neoplasm Proteins; D002336:Carnosine; D001052:Apoferritins; C522928:CNDP1 protein, human; D004150:Dipeptidases; D002118:Calcium