Investigation of the Ovarian and Prostate Cancer Peptidome for Candidate Early Detection Markers Using a Novel Nanoparticle Biomarker Capture Technology

Abstract

Current efforts to identify protein biomarkers of disease use mainly mass spectrometry (MS) to analyze tissue and blood specimens. The low-molecular-weight “peptidome” is an attractive information archive because of the facile nature by which the low-molecular-weight information freely crosses the endothelial cell barrier of the vasculature, which provides opportunity to measure disease microenvironment-associated protein analytes secreted or shed into the extracellular interstitium and from there into the circulation. However, identifying useful protein biomarkers (peptidomic or not) which could be useful to detect early detection/monitoring of disease, toxicity, doping, or drug abuse has been severely hampered because even the most sophisticated, high-resolution MS technologies have lower sensitivities than those of the immunoassays technologies now routinely used in clinical practice. Identification of novel low abundance biomarkers that are indicative of early-stage events that likely exist in the sub-nanogram per milliliter concentration range of known markers, such as prostate-specific antigen, cannot be readily detected by current MS technologies. We have developed a new nanoparticle technology that can, in one step, capture, concentrate, and separate the peptidome from high-abundance blood proteins. Herein, we describe an initial pilot study whereby the peptidome content of ovarian and prostate cancer patients is investigated with this method. Differentially abundant candidate peptidome biomarkers that appear to be specific for early-stage ovarian and prostate cancer have been identified and reveal the potential utility for this new methodology

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Acknowledgments

The authors appreciate the generous support of Dr. Vikas Chandhoke and the Department of Life Sciences at George Mason University. This work was partly supported by the Italian Istituto Superiore di Sanita` in the framework Italy/USA cooperation agreement between the U.S. Department of Health and Human Services, George Mason University, and the Italian Ministry of Public Health. This work was partially supported by the U.S. Department of Energy grant no. 201270.

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Correspondence to Emanuel F. Petricoin III.

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Claudia Fredolini and Francesco Meani equally contributed to this work.

Guest Editors: Rao S. Rapaka, Lloyd D. Fricker, and Jonathan V. Sweedler

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Fredolini, C., Meani, F., Luchini, A. et al. Investigation of the Ovarian and Prostate Cancer Peptidome for Candidate Early Detection Markers Using a Novel Nanoparticle Biomarker Capture Technology. AAPS J 12, 504–518 (2010). https://doi.org/10.1208/s12248-010-9211-3

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Key words

  • Peptidome
  • Cancer
  • Biomarker
  • Nanoparticle
  • Mass spectrometry