This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ye, B. Articles by Cramer, D. W. Search for Related Content PubMed PubMed Citation Articles by Ye, B. Articles by Cramer, D. W. Related Collections Commentary

Proteomic-Based Discovery and Characterization of Glycosylated Eosinophil-Derived Neurotoxin and COOH-Terminal Osteopontin Fragments for Ovarian Cancer in Urine

Authors' Affiliations: ¹ Laboratory of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, and ² Renal and Pathology Division, Brigham and Women's Hospital, Harvard Medical School, Dana-Farber Cancer Center; ³ Biostatistics Center and ⁴ Reproductive Endocrine Unit Laboratory, Massachusetts General Hospital, Boston, Massachussetts; and ⁵ Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland

Requests for reprints: Bin Ye, Laboratory of Gynecologic Oncology, Brigham and Women's Hospital, Harvard Medical School, Dana-Farber Cancer Center, 221 Longwood Avenue, LMRC-610B, Boston, MA 02115. Phone: 617-732-6976; Fax: 617-264-5248; E-mail: Bye{at}partners.org.

Purpose: The objective was to identify and characterize low molecular weight proteins/peptides in urine and their posttranslational modifications that might be used as a screening tool for ovarian cancer.

Experimental Design: Urine samples collected preoperatively from postmenopausal women with ovarian cancer and benign conditions and from nonsurgical controls were analyzed by surface-enhanced laser desorption/ionization mass spectrometry and two-dimensional gel electrophoresis. Selected proteins from mass profiles were purified by chromatography and followed by liquid chromatography-tandem mass spectrometry sequence analysis. Specific antibodies were generated for further characterization, including immunoprecipitation and glycosylation. Quantitative and semiquantitative ELISAs were developed for preliminary validation in patients of 128 ovarian cancer, 52 benign conditions, 44 other cancers, and 188 healthy controls.

Results: A protein (m/z 17,400) with higher peak intensities in cancer patients than in benign conditions and controls was identified and subsequently defined as eosinophil-derived neurotoxin (EDN). A glycosylated form of EDN was specifically elevated in ovarian cancer patients. A cluster of COOH-terminal osteopontin was identified from two-dimensional gels of urine from cancer patients. Modified forms EDN and osteopontin fragments were elevated in early-stage ovarian cancers and a combination of both resulted to 93% specificity and 72% sensitivity.

Conclusions: Specific elevated posttranslationally modified urinary EDN and osteopontin COOH-terminal fragments in ovarian cancer might lead to potential noninvasive screening tests for early diagnosis. Urine with less complexity than serum and relatively high thermodynamic stability of peptides or metabolites is a promising study medium for discovery of the novel biomarkers which may present in many nonurinary tract neoplastic diseases.

Commentary

Ovarian Cancer Biomarkers in Urine

Ann F. Chambers and Barbara C. Vanderhyden
Clin. Cancer Res. 2006 12: 323-327. [Full Text] [PDF]

This article has been cited by other articles:

				I. Visintin, Z. Feng, G. Longton, D. C. Ward, A. B. Alvero, Y. Lai, J. Tenthorey, A. Leiser, R. Flores-Saaib, H. Yu, et al. Diagnostic Markers for Early Detection of Ovarian Cancer Clin. Cancer Res., February 15, 2008; 14(4): 1065 - 1072. [Abstract] [Full Text] [PDF]

				D. Jackson, R. A. Craven, R. C. Hutson, I. Graze, P. Lueth, R. P. Tonge, J. L. Hartley, J. A. Nickson, S. J. Rayner, C. Johnston, et al. Proteomic Profiling Identifies Afamin as a Potential Biomarker for Ovarian Cancer Clin. Cancer Res., December 15, 2007; 13(24): 7370 - 7379. [Abstract] [Full Text] [PDF]

				J. Eriksson, C. Woschnagg, E. Fernvik, and P. Venge A SELDI-TOF MS study of the genetic and post-translational molecular heterogeneity of eosinophil cationic protein J. Leukoc. Biol., December 1, 2007; 82(6): 1491 - 1500. [Abstract] [Full Text] [PDF]

				R. Saldova, L. Royle, C. M Radcliffe, U. M Abd Hamid, R. Evans, J. N Arnold, R. E Banks, R. Hutson, D. J Harvey, R. Antrobus, et al. Ovarian Cancer is Associated with Changes in Glycosylation in Both Acute-Phase Proteins and IgG Glycobiology, December 1, 2007; 17(12): 1344 - 1356. [Abstract] [Full Text] [PDF]

				D. Petrik, P. W. Lavori, H. Cao, Y. Zhu, P. Wong, E. Christofferson, M. J. Kaplan, H. A. Pinto, P. Sutphin, A. C. Koong, et al. Plasma Osteopontin Is an Independent Prognostic Marker for Head and Neck Cancers J. Clin. Oncol., November 20, 2006; 24(33): 5291 - 5297. [Abstract] [Full Text] [PDF]

				T. Pisitkun, R. Johnstone, and M. A. Knepper Discovery of Urinary Biomarkers Mol. Cell. Proteomics, October 1, 2006; 5(10): 1760 - 1771. [Abstract] [Full Text] [PDF]

				A. F. Chambers and B. C. Vanderhyden Ovarian Cancer Biomarkers in Urine Clin. Cancer Res., January 15, 2006; 12(2): 323 - 327. [Full Text] [PDF]