Affiliations: NIH-Howard Hughes Research Scholar, Howard Hughes
Medical Institute, Bethesda, MD 20814, USA | FDA-NCI Clinical Proteomics Program, Office of the
Director, Center for Biologics Evaluation and Research, Food and Drug
Administration, Bethesda, MD 20892, USA | FDA-NCI Clinical Proteomics Program, Laboratory of
Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD
20892, USA | National Ovarian Cancer Early Detection Program,
Northwestern University Medical School, Chicago, IL 60611, USA
Note: [] Corresponding author: Arpita I. Mehta, 10 Center Drive, Bldg 10,
Room 2A33, Laboratory of Pathology, NCI, NIH, Bethesda, MD 20892-1500, USA.
Tel.: +1 847 530 8230; Fax: +1 301 480 0853; E-mail: [email protected]
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.
