Volume 19, Issue 1 104879 pp. 1-10
Article
Open Access

Biomarker Amplification by Serum Carrier Protein Binding

Arpita I. Mehta

Corresponding Author

Arpita I. Mehta

NIH-Howard Hughes Research Scholar Howard Hughes Medical Institute Bethesda MD 20814, USA , nih.gov

FDA-NCI Clinical Proteomics Program Office of the Director Center for Biologics Evaluation and Research Food and Drug Administration Bethesda MD 20892, USA , fda.gov

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Sally Ross

Sally Ross

FDA-NCI Clinical Proteomics Program Office of the Director Center for Biologics Evaluation and Research Food and Drug Administration Bethesda MD 20892, USA , fda.gov

FDA-NCI Clinical Proteomics Program Laboratory of Pathology Center for Cancer Research National Cancer Institute Bethesda MD 20892, USA , cancer.gov

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Mark S. Lowenthal

Mark S. Lowenthal

FDA-NCI Clinical Proteomics Program Office of the Director Center for Biologics Evaluation and Research Food and Drug Administration Bethesda MD 20892, USA , fda.gov

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Vincent Fusaro

Vincent Fusaro

FDA-NCI Clinical Proteomics Program Office of the Director Center for Biologics Evaluation and Research Food and Drug Administration Bethesda MD 20892, USA , fda.gov

FDA-NCI Clinical Proteomics Program Laboratory of Pathology Center for Cancer Research National Cancer Institute Bethesda MD 20892, USA , cancer.gov

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David A. Fishman

David A. Fishman

National Ovarian Cancer Early Detection Program Northwestern University Medical School Chicago IL 60611, USA , northwestern.edu

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Emanuel F. Petricoin III

Emanuel F. Petricoin III

FDA-NCI Clinical Proteomics Program Office of the Director Center for Biologics Evaluation and Research Food and Drug Administration Bethesda MD 20892, USA , fda.gov

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Lance A. Liotta

Lance A. Liotta

FDA-NCI Clinical Proteomics Program Office of the Director Center for Biologics Evaluation and Research Food and Drug Administration Bethesda MD 20892, USA , fda.gov

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First published: 12 June 2013
Citations: 163

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.

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