Elevation of CA19-9 related novel marker, Core 1 Sialyl Lewis A, in sera of adenocarcinoma patients verified by a SRM based method.

We have attempted to identify a novel glycan tumor marker. Pyridylaminated (PA) O-glycans were prepared from sera, and the comparing the serum O-glycan profiles from healthy controls with those of corresponding O-glycan profiles were constructed by HPLC separation. By cancer patients, we identified a marker candidate, core 1 sialyl Lewis A (NeuAc alpha 2-3Gal beta 1-3 (Fuc alpha 1-4) GlcNAc beta 1-3 Gal) (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 (d(4)-PA) glycan, as an internal standard. The analyte (d(0)-PA-C1SLA) and the internal standard (d(4)-PA-C1SLA) were subjected to SRM analyses after two types of HPLC separation. Serum levels of C1SLA, determined as the relative ratio to total 0-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.