Elevation of CA19-9-Related Novel Marker, Core 1 Sialyl Lewis A, in Sera of Adenocarcinoma Patients Verified by a SRM-Based Method.
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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通过基于 SRM 的方法验证腺癌患者血清中 CA19-9 相关新型标记物 Core 1 Sialyl Lewis A 的升高。
DOI：
10.1021/acs.jproteome.5b00893
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发表时间：
2016
影响因子：
4.4
通讯作者：
Miyamoto Y.
中科院分区：
文献类型：
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作者：
Tanaka-Okamoto M;Yabu M;Mukai M;Takahashi H;Fujiwara Y;Ohue M;Kamada Y;Miyoshi E;Miyamoto Y.
我们试图鉴定一种新的糖链肿瘤标记物。从血清中制备了吡啶层状(PA)O-葡聚糖，并通过高效液相色谱分离构建了相应的O-葡聚糖图谱。通过比较健康对照组和癌症患者的血清O-糖链图谱，我们确定了一个标记候选，核心1唾液酸路易斯A(NeuAcα2-3Galβ1-3(Fucα1-4)GlcNAcβ1-3Gal)(简称C1SLA)，其浓度似乎与CA19-9的值呈弱相关。为了定量这种多糖，我们开发了一种选择性反应监测(SRM)分析方法，它使用稳定的同位素-四氢标记吡啶氨基(d4-PA)多糖作为内标。分析物(d0-PA-C1SLA)和内标物(d4-PA-C1SLA)在两种高效液相色谱分离后进行SRM分析。然后测量血清C1SLA水平，以与总O-糖链的相对比率来确定。这些分析表明：(1)C1SLA是一种CA19-9相关的糖链；(2)正常对照的C1SLA平均值为3.41ppm；(3)C1SLA水平在II-IV期胃癌(P=0.0036)以及胰腺癌(P<；0.0001)中显著高于正常对照组；(4)C1SLA与CA19-9的关系因癌症而异，以及(V)C1SLA可作为癌症的辅助诊断指标。
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.