1. Elevation of CA19-9-Related Novel Marker, Core 1 Sialyl Lewis A, in Sera of Adenocarcinoma Patients Verified by a SRM-Based Method
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Mikio Mukai, Miki Tanaka-Okamoto, Masahiko Yabu, Yoshihiro Kamada, Eiji Miyoshi, Masayuki Ohue, Hidenori Takahashi, Yasuhide Miyamoto, and Yoshiyuki Fujiwara
- Subjects
Male ,0301 basic medicine ,Analyte ,Glycan ,CA-19-9 Antigen ,Molecular Sequence Data ,Oligosaccharides ,Adenocarcinoma ,Digestive System Neoplasms ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Lewis Blood Group Antigens ,Tandem Mass Spectrometry ,Carbohydrate Conformation ,medicine ,Humans ,Chromatography, High Pressure Liquid ,Neoplasm Staging ,Tumor marker ,Chromatography ,biology ,Selected reaction monitoring ,Cancer ,General Chemistry ,Middle Aged ,Sialyl-Lewis A ,medicine.disease ,030104 developmental biology ,Carbohydrate Sequence ,chemistry ,Case-Control Studies ,biology.protein ,Female ,CA19-9 - 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. more...
- Published
- 2015
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