title: A serum glycomics approach to breast cancer biomarkers.
abstract: Because the glycosylation of proteins is known to change in tumor cells during the development of breast cancer, a glycomics approach is used here to find relevant biomarkers of breast cancer. These glycosylation changes are known to correlate with increasing tumor burden and poor prognosis. Current antibody-based immunochemical tests for cancer biomarkers of ovarian (CA125), breast (CA27.29 or CA15-3), pancreatic, gastric, colonic, and carcinoma (CA19-9) target highly glycosylated mucin proteins. However, these tests lack the specificity and sensitivity for use in early detection. This glycomics approach to find glycan biomarkers of breast cancer involves chemically cleaving oligosaccharides (glycans) from glycosylated proteins that are shed or secreted by breast cancer tumor cell lines. The resulting free glycan species are analyzed by MALDI-FT-ICR MS. Further structural analysis of the glycans can be performed in FTMS through the use of tandem mass spectrometry with infrared multiphoton dissociation. Glycan profiles were generated for each cell line and compared. These methods were then used to analyze sera obtained from a mouse model of breast cancer and a small number of serum samples obtained from human patients diagnosed with breast cancer or patients with no known history of breast cancer. In addition to the glycosylation changes detected in mice as mouse mammary tumors developed, glycosylation profiles were found to be sufficiently different to distinguish patients with cancer from those without. Although the small number of patient samples analyzed so far is inadequate to make any legitimate claims at this time, these promising but very preliminary results suggest that glycan profiles may contain distinct glycan biomarkers that may correspond to glycan "signatures of cancer."
authors.affiliation: Department of Chemistry, University of California, Davis, California 95616, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Kirmiz
authors.forename: Bensheng
authors.initials: B
authors.lastname: Li
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: An
authors.forename: Brian H
authors.initials: BH
authors.lastname: Clowers
authors.forename: Helen K
authors.initials: HK
authors.lastname: Chew
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
authors.forename: Anthony
authors.initials: A
authors.lastname: Ferrige
authors.forename: Robert
authors.initials: R
authors.lastname: Alecio
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Borowsky
authors.forename: Shola
authors.initials: S
authors.lastname: Sulaimon
authors.forename: Carlito B
authors.initials: CB
authors.lastname: Lebrilla
authors.forename: Suzanne
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000737:chemistry*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D006023:Glycoproteins / Q000097:blood / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008875:Middle Aged; D011134:Polysaccharides / Q000097:blood* / Q000737:chemistry; D025341:Principal Component Analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013347:Subcellular Fractions; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D006023:Glycoproteins; D011134:Polysaccharides