Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients.
The molecular analysis of serum is an important field for the definition of potential diagnostic markers or disease-related protein alterations. Novel proteomic technologies such as the mass spectrometric-based surface-enhanced laser desorption/ionization (SELDI) ProteinChip technique facilitate a rapid and reproducible analysis of such protein mixtures and affords the researcher a new dimension in the search for biomarkers of disease. Here, we have applied this technology to the study of a cohort of serum samples from well-characterized renal cell carcinoma patients for the identification of such proteins by comparison to healthy controls. We detected and characterized haptoglobin 1 alpha and serum amyloid alpha-1 (SAA-1) as disease related, in addition to an as-yet-unidentified marker of 10.84 kDa. Of particular note is the detection of multiple variants of SAA-1 in multiplex that have not been described in the sera of cancer patients. SAA-1 is detected as full-length protein, des-Arginine and des-Arginine/des-Serine variants at the N terminus by SELDI. In addition, we could also detect a low-abundant variant minus the first five N-terminal amino acids. Such variants may impact the function of the protein. We conclude the technique to be a reproducible, fast and simple mode for the discovery and analysis of marker proteins of disease in serum.
Tolson
Jonathan
J
Section for Transplantation Immunology and Immunohematology, University of Tuebingen, Waldhoernlestrasse 22, 72072 Tuebingen, Germany.
Bogumil
Ralf
R
Brunst
Elke
E
Beck
Hermann
H
Elsner
Raimund
R
Humeny
Andreas
A
Kratzin
Hartmut
H
Deeg
Martin
M
Kuczyk
Markus
M
Mueller
Gerhard A
GA
Mueller
Claudia A
CA
Flad
Thomas
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001053:Apolipoproteins / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006242:Haptoglobins / Q000032:analysis; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis; D000685:Serum Amyloid A Protein; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D001053:Apolipoproteins; D001798:Blood Proteins; D006242:Haptoglobins; D000685:Serum Amyloid A Protein