title: Elevation of CA19-9-Related Novel Marker, Core 1 Sialyl Lewis A, in Sera of Adenocarcinoma Patients Verified by a SRM-Based Method.
abstract: We have attempted to identify a novel glycan tumor marker. Pyridylaminated (PA) O-glycans were prepared from sera, and the corresponding O-glycan profiles were constructed by HPLC separation. By comparing the serum O-glycan profiles from healthy controls with those of cancer patients, we identified a marker candidate, core 1 sialyl Lewis A (NeuAcα2-3Galβ1-3(Fucα1-4)GlcNAcβ1-3Gal) (abbreviated C1SLA), whose concentration appeared to be weakly correlated with CA19-9 values. To quantify this glycan, we developed a selected reaction monitoring (SRM) assay that used a stable isotope, tetradeuterium-labeled pyridylamino (d4-PA) glycan, as an internal standard. The analyte (d0-PA-C1SLA) and the internal standard (d4-PA-C1SLA) were subjected to SRM analyses after two types of HPLC separation. Serum levels of C1SLA, determined as the relative ratio to total O-glycans, were then measured. These analyses revealed that (i) C1SLA is a CA19-9-related glycan, (ii) the mean value of C1SLA in normal controls is 3.41 ppm, (iii) the level of C1SLA was significantly higher in samples of stages II-IV stomach cancers (P = 0.0036) as well as pancreatic cancers (P < 0.0001) compared to that of normal controls, (iv) the relationship between C1SLA and CA19-9 varies from poor to weak depending on the cancer, and (v) C1SLA could be valuable as a diagnostic adjunct for cancer.
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 Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases , 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yabu
authors.forename: Mikio
authors.initials: M
authors.lastname: Mukai
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohue
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University, Graduate School of Medicine , 1-7 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University, Graduate School of Medicine , 1-7 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
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: D000230:Adenocarcinoma / Q000097:blood* / Q000145:classification* / Q000473:pathology; D018395:CA-19-9 Antigen / Q000097:blood* / Q000302:isolation & purification; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004067:Digestive System Neoplasms / Q000097:blood* / Q000473:pathology; D005260:Female; D006801:Humans; D007983:Lewis Blood Group Antigens; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D009844:Oligosaccharides / Q000097:blood* / Q000302:isolation & purification; D053719:Tandem Mass Spectrometry
chemical_list: D018395:CA-19-9 Antigen; D007983:Lewis Blood Group Antigens; C494219:Lewis a oligosaccharide; D009844:Oligosaccharides
keywords: CA19-9; Carbohydrate; SRM; sialyl Lewis A; tumor marker