Affiliations: W.M. Keck FT-ICR Mass Spectrometry Laboratory, Mayo
Proteomics Research Center, Rochester, MN, USA | Department of Biochemistry and Molecular Biology, Mayo
Clinic College of Medicine, Rochester, MN, USA | Division of Experimental Pathology, Mayo Clinic
College of Medicine, Rochester, MN, USA | Department of Obstetrics and Gynecology, Mayo Clinic
College of Medicine, Rochester, MN, USA | Division of Biostatistics, Mayo Clinic College of
Medicine, Rochester, MN 55905, USA
Note: [] Corresponding author: David C. Muddiman, Ph.D., Medical Science
Building 3-115, Mayo Clinic College of Medicine, 200 First Street, SW,
Rochester, MN 55905, USA. Tel.: +1 507 284 1997; Fax: +1 507 284 9261; E-mail:
[email protected]
Abstract: Treatment of cancer patients is greatly facilitated by detection of
the cancer prior to metastasis. One of the obstacles to early cancer detection
is the lack of availability of biomarkers with sufficient specificity. With
modern differential proteomic techniques, the potential exists to identify high
specificity cancer biomarkers. We have delineated a set of protocols for the
isolation and identification of serum biomarkers for ovarian cancer that exist
in the low molecular weight serum fraction. After isolation of the low
molecular weight fraction by ultrafiltration, the potential biomarkers are
separated by reversed phase nano liquid chromatography. Detection via TOF or
FT-ICR yields a data set for each sample. We compared stage III/IV ovarian
cancer serum with postmenopausal age-matched controls. Using bioinformatics
tools developed at Mayo, we normalized each sample for intensity and
chromatographic alignment. Normalized data sets are subsequently compared and
potential biomarkers identified. Several candidate biomarkers were found. One
of these contains the sequence of fibrinopeptide-A known to be elevated in many
types of cancer including ovarian cancer. The protocols utilized will be
examined and would be applicable to a wide variety of cancers or disease
states.
Keywords: ovarian cancer, biomarkers, bioinformatics, serum, FT-ICR, TOF, mass spectrometry
Journal: Disease Markers, vol. 19, no. 4-5, pp. 239-249, 2003,2004
