title: Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients.
abstract: 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.
authors.affiliation: Section for Transplantation Immunology and Immunohematology, University of Tuebingen, Waldhoernlestrasse 22, 72072 Tuebingen, Germany.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Tolson
authors.forename: Ralf
authors.initials: R
authors.lastname: Bogumil
authors.forename: Elke
authors.initials: E
authors.lastname: Brunst
authors.forename: Hermann
authors.initials: H
authors.lastname: Beck
authors.forename: Raimund
authors.initials: R
authors.lastname: Elsner
authors.forename: Andreas
authors.initials: A
authors.lastname: Humeny
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kratzin
authors.forename: Martin
authors.initials: M
authors.lastname: Deeg
authors.forename: Markus
authors.initials: M
authors.lastname: Kuczyk
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Mueller
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Mueller
authors.forename: Thomas
authors.initials: T
authors.lastname: Flad
mesh_terms: 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
chemical_list: D001053:Apolipoproteins; D001798:Blood Proteins; D006242:Haptoglobins; D000685:Serum Amyloid A Protein