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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• 作者：Miki Tanaka-Okamoto ; Masahiko Yabu ; Mikio Mukai ; Hidenori Takahashi ; Yoshiyuki Fujiwara ; Masayuki Ohue ; Yoshihiro Kamada ; Eiji Miyoshi ; Yasuhide Miyamoto
• 刊名：Journal of Proteome Research
• 出版年：2016
• 出版时间：January 4, 2016
• 年：2016
• 卷：15
• 期：1
• 页码：152-165
• 全文大小：576K
• ISSN：1535-3907

文摘

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.