title: Biomarker amplification by serum carrier protein binding.
abstract: Mass spectroscopic analysis of the low molecular mass (LMM) range of the serum/plasma proteome is a rapidly emerging frontier for biomarker discovery. This study examined the proportion of LMM biomarkers, which are bound to circulating carrier proteins. Mass spectroscopic analysis of human serum following molecular mass fractionation, demonstrated that the majority of LMM biomarkers exist bound to carrier proteins. Moreover, the pattern of LMM biomarkers bound specifically to albumin is distinct from those bound to non-albumin carriers. Prominent SELDI-TOF ionic species (m/z 6631.7043) identified to correlate with the presence of ovarian cancer were amplified by albumin capture. Several insights emerged: a) Accumulation of LMM biomarkers on circulating carrier proteins greatly amplifies the total serum/plasma concentration of the measurable biomarker, b) The total serum/plasma biomarker concentration is largely determined by the carrier protein clearance rate, not the unbound biomarker clearance rate itself, and c) Examination of the LMM species bound to a specific carrier protein may contain important diagnostic information. These findings shift the focus of biomarker detection to the carrier protein and its biomarker content.
authors.affiliation: Howard Hughes Medical Institute, Bethesda, MD 20814, USA. arpita.mehta@tufts.edu
authors.forename: Arpita I
authors.initials: AI
authors.lastname: Mehta
authors.forename: Sally
authors.initials: S
authors.lastname: Ross
authors.forename: Mark S
authors.initials: MS
authors.lastname: Lowenthal
authors.forename: Vincent
authors.initials: V
authors.lastname: Fusaro
authors.forename: David A
authors.initials: DA
authors.lastname: Fishman
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: Lance A
authors.initials: LA
authors.lastname: Liotta
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood*; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D008657:Metabolic Clearance Rate; D008970:Molecular Weight; D011485:Protein Binding; D020543:Proteome / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D020543:Proteome; D012709:Serum Albumin