title: Early diagnostic protein biomarkers for breast cancer: how far have we come?
abstract: Many studies have used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to search for blood-based proteins that are related to the presence of breast cancer. We review the biomarkers discovered or targeted measured by these methods and discuss the strengths and weaknesses of these studies. We highlight two proteins that were most often related to breast cancer: C3a des-arginine anaphylatoxin (C3adesArg) (molecular weight: 8,938 Da) and fragments of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4). In addition, we elaborate on three important methodological aspects related to these studies: protein identification, specificity of the markers, and disease heterogeneity. Finally, we propose some points to be addressed in future studies. These include the use of other analytical measurement techniques, need of protein identification, the importance of identical sample handling protocols for cases and controls, and the stratification of the results according to molecular subtypes and stages of breast cancer. Ultimately this may lead to the discovery of new and valid breast cancer specific biomarkers.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
authors.forename: Annemieke W J
authors.initials: AW
authors.lastname: Opstal-van Winden
authors.forename: Roel C H
authors.initials: RC
authors.lastname: Vermeulen
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D015926:Complement C3a / Q000737:chemistry / Q000378:metabolism; D055088:Early Detection of Cancer; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D053491:Proteinase Inhibitory Proteins, Secretory / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D006023:Glycoproteins; C091236:ITIH4 protein, human; D010446:Peptide Fragments; D053491:Proteinase Inhibitory Proteins, Secretory; D015926:Complement C3a