title: Various sulfated carbohydrate tumor marker candidates identified by focused glycomic analyses.
abstract: Glycomic analysis focused on sulfated O-glycans was performed to identify novel serum carbohydrate tumor markers. Sulfated glycans were enriched by α-neuraminidase digestion of pyridylaminated glycans prepared from sera, followed by anion exchange chromatography. Sulfated O-glycan profiles were constructed by two types of high performance liquid chromatography separation. Comparison of the profiles from 20 healthy controls with those of 11 gastric and 9 pancreatic cancer patients identified 14 marker candidates. The structures of these candidates were precisely analyzed using various methods including enzymatic digestion and mass spectrometry. The candidates comprised 9 core1 and 5 core2 glycans. All these candidates were monosulfated, and 11 were also mono- or difucosylated, and included various determinants such as 6-sulfo type2 lactosamine, 6-sulfo Lewis X, 6-sulfo Lewis Y, 3'-sulfo type1 lactosamine and 3'-sulfo Lewis A. Furthermore, among the core1 glycans, five candidates displayed a type1 and type2 lactosamine hybrid backbone. The levels of these candidate glycans in the sera from all 40 subjects were quantified using a selected reaction monitoring assay. These analyses revealed: (i) the levels of all candidates were elevated in sera of at least one or more patients; (ii) core1 candidates having type1-type2 hybrid backbones with 6-sulfo Lewis X, 6-sulfo type2 lactosamine or 3'-sulfo Lewis A were elevated in sera of variety of patients; and (iii) levels of the candidates varied widely among patients, suggesting analysis of multiple candidates will be an effective means of screening various cancers. To fully evaluate the clinical utility of these candidates, a further verification study is required.
authors.affiliation: Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Tanaka-Okamoto
authors.affiliation: Department of Multiphase Health Screening, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Mukai
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohue
authors.affiliation: Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Miyamoto
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D005260:Female; D054794:Glycomics; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000737:chemistry; D011134:Polysaccharides / Q000097:blood*; D013274:Stomach Neoplasms / Q000097:blood* / Q000737:chemistry; D013431:Sulfates / Q000097:blood / Q000737:chemistry
chemical_list: D014408:Biomarkers, Tumor; D002241:Carbohydrates; D011134:Polysaccharides; D013431:Sulfates
keywords: SRM; carbohydrate; sulfate; tumor marker