title: Improved classification of breast cancer peptide and protein profiles by combining two serum workup procedures.
abstract: OBJECTIVE
  Detection of breast cancer at early stage increases patient's survival. Mass spectrometry-based protein analysis of serum samples is a promising approach to obtain biomarker profiles for early detection. A combination of commonly applied solid-phase extraction procedures for clean-up may increase the number of detectable peptides and proteins. In this study, we have evaluated whether the classification performance of breast cancer profiles improves by using two serum workup procedures.
  
  
  METHODS
  Serum samples from 105 breast cancer patients and 202 healthy volunteers were processed according to a standardized protocol implemented on a high-end liquid-handling robot. Peptide and protein enrichments were carried out using weak-cation exchange (WCX) and reversed-phase (RP) C18 magnetic beads. Profiles were acquired on a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer. In this way, two different biomarker profiles were obtained for each serum sample, yielding a WCX- and RPC18-dataset.
  
  
  RESULTS
  The profiles were statistically evaluated with double cross-validation. Classification results of WCX- and RPC18-datasets were determined for each set separately and for the combination of both sets. Sensitivity and specificity were 82 and 87 % (WCX) and 73 and 93 % (RPC18) for the individual workup procedures. These values increased up to 84 and 95 %, respectively, upon combining the data.
  
  
  CONCLUSIONS
  It was found that MALDI-TOF peptide and protein profiles can be used for classification of breast cancer with high sensitivity and specificity. The classification performance even improved when two workup procedures were applied, since these provide a greater number of features (proteins).
authors: Department of Surgery, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. b.velstra@lumc.nl
authors: Berit
authors: B
authors: Velstra
authors: Yuri E M
authors: YE
authors: van der Burgt
authors: Bart J
authors: BJ
authors: Mertens
authors: Wilma E
authors: WE
authors: Mesker
authors: André M
authors: AM
authors: Deelder
authors: Rob A E M
authors: RA
authors: Tollenaar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000097:blood* / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010455:Peptides / Q000097:blood*; D040081:Protein Array Analysis / Q000379:methods; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D009363:Neoplasm Proteins; D010455:Peptides