Proteomic analysis of cerebrospinal fluid discriminates malignant and nonmalignant disease of the central nervous system and identifies specific protein markers.
CNS diseases are often accompanied by changes in the protein composition of cerebrospinal fluid (CSF). SELDI-TOF-MS provides an approach for identifying specific protein markers of disease in biological fluids. We compared the CSF proteomes from patients with neoplastic and reactive/inflammatory CNS diseases to identify potential biomarkers. SELDI-TOF-MS was performed on CSF derived from lumbar puncture of 32 patients, including 10 with CNS malignancies, 12 with inflammatory or reactive conditions, and 10 with unknown CNS disease. Using the SAX-2 (strong anionic exchange) chip, we uncovered three conserved protein peak ranges within each disease category. For neoplastic diseases, we identified conserved peaks at 7.5-8.0 kDa (9/10 samples), 15.1-15.9 kDa (8/10 samples), and 30.0-32.0 kDa (5/10 samples). In reactive/inflammatory diseases, conserved peaks were found at 6.7-7.1 kDa (10/12 samples), 11.5-11.9 kDa (12/12 samples), and 13.3-13.7 kDa (9/12 samples). A protein from the 30.0 to 32.0 kDa peak range found in neoplastic CSF was identified by MALDI analysis as carbonic anhydrase, a protein overexpressed in many malignancies including high-grade gliomas. Similarly, cystatin C was identified in the 13.3-13.7 kDa peak range in non-neoplastic CSF and was most prominent in inflammatory conditions. Our approach provides a rational basis for identifying biomarkers that could be used for detection, diagnosis, and monitoring of CNS diseases.
Khwaja
Fatima W
FW
Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA.
Nolen
John David Larkin
JD
Mendrinos
Savaas E
SE
Lewis
Melinda M
MM
Olson
Jeffrey J
JJ
Pohl
Jan
J
Van Meir
Erwin G
EG
Ritchie
James C
JC
Brat
Daniel J
DJ
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001932:Brain Neoplasms / Q000737:chemistry*; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid*; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins