二维凝胶电泳和质谱表征的靶标癌症生物标志物的 N-聚糖结构,Analytica Chimica Acta

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二维凝胶电泳和质谱表征的靶标癌症生物标志物的 N-聚糖结构
Analytica Chimica Acta ( IF 5.7 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.aca.2020.04.063
Sha Liu ₁ , Xiaoteng Jiang ₁ , Zhi Shang ₁ , Yin Ji ₂ , Huiyu Wang ₁ , Zeyuan Wang ₁ , Peng Wang ₂ , Yan Zhang ₃ , Hua Xiao ₁

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糖蛋白是癌症的重要生物标志物，而大多数糖蛋白组学生物标志物由于其未表征的聚糖结构而具有低灵敏度和特异性。AZGP1 是肺癌唾液诊断的潜在生物标志物，在本研究中用作模型糖蛋白以进行方法开发。我们最初使用凝集素亲和层析分析了唾液 N-糖蛋白组，并鉴定了 300 多种 N-糖蛋白，包括 AZGP1。AZGP1的7个凝胶点通过二维凝胶电泳分离，并通过二维蛋白质印迹和质谱进一步证实。这些点中 AZGP1 的异构聚糖结构在组成水平和结构水平上都被系统地表征。我们的结果揭示了唾液 AZGP1 的 10 种聚糖组成，包括 Asn128 上的核心岩藻糖基化聚糖和 Asn109 和 Asn112 上的唾液酸化聚糖。我们进一步比较了肺癌组和对照组唾液AZGP1的聚糖结构。因此，分别成功揭示了 14 个和 7 个潜在的聚糖结构。总共鉴定并表征了 AZGP1 的 15 种聚糖组成和 22 种潜在的聚糖结构，包括一些具有相同组成的不同结构。特别是，5 种潜在的聚糖结构被鉴定为肺癌独特的特征。我们开发的策略有望彻底鉴定目标糖蛋白生物标志物上的聚糖结构。对其聚糖结构的深入表征将最终提高其对癌症检测的敏感性和特异性。

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N-glycan structures of target cancer biomarker characterized by two-dimensional gel electrophoresis and mass spectrometry

Glycoproteins are important biomarkers for cancers, while most glycoproteomics biomarkers suffering from low sensitivity and specificity due to their uncharacterized glycan structures. AZGP1 is a potential biomarker for salivary diagnostics of lung cancer, which is used as a model glycoprotein in this study for method development. We initially analyzed salivary N-glycoproteome by using lectin affinity chromatography and more than 300 N-glycoproteins were identified, including AZGP1. 7 gel spots of AZGP1 were resolved by two-dimensional gel electrophoresis and further confirmed by two-dimensional western blot as well as mass spectrometry. The isomeric glycan structures of AZGP1 in these spots were systematically characterized both at composition level and at structure level. Our results revealed 10 glycan compositions for salivary AZGP1, including core fucosylated glycans on Asn128 and sialylated glycans on Asn109 and Asn112. We further compared the glycan structures of salivary AZGP1 from lung cancer group and control group. Accordingly, 14 and 7 potential glycan structures were successfully revealed, respectively. In total, 15 glycan compositions and 22 potential glycan structures were identified and characterized for AZGP1, including some different structures with the same compositions. In particular, 5 potential glycan structures were identified as lung cancer unique signatures. Our developed strategy holds promise for thorough identification of glycan structures on a target glycoprotein biomarker. In-depth characterization of its glycan structures will ultimately enhance its sensitivity and specificity for cancer detection.

更新日期：2020-08-01

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