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Disease Markers
Volume 19 (2003), Issue 1, Pages 1-10
http://dx.doi.org/10.1155/2003/104879

Biomarker Amplification by Serum Carrier Protein Binding

Arpita I. Mehta,1,2 Sally Ross,2,3 Mark S. Lowenthal,2 Vincent Fusaro,2,3 David A. Fishman,4 Emanuel F. Petricoin III,2 and Lance A. Liotta2

1NIH-Howard Hughes Research Scholar, Howard Hughes Medical Institute, Bethesda, MD 20814, USA
2FDA-NCI Clinical Proteomics Program, Office of the Director, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
3FDA-NCI Clinical Proteomics Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
4National Ovarian Cancer Early Detection Program, Northwestern University Medical School, Chicago, IL 60611, USA

Received 16 December 2003; Accepted 16 December 2003

Copyright © 2003 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.