State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing 210042, China.
J Proteome Res. 2022 Jul 1;21(7):1589-1602. doi: 10.1021/acs.jproteome.1c00701. Epub 2022 Jun 17.
Aberrant protein -glycosylation is a cancer hallmark, which has great potential for cancer detection. However, large-scale and in-depth analysis of -glycosylation remains challenging because of its high heterogeneity, complexity, and low abundance. Human saliva is an attractive diagnostic body fluid, while few efforts explored its -glycoproteome for lung cancer. Here, we utilized a zwitterionic-hydrophilic interaction chromatography-based strategy to specifically enrich salivary glycopeptides. Through quantitative proteomics analysis, 1492 and 1234 intact -glycopeptides were confidently identified from pooled saliva samples of 10 subjects in the nonsmall-cell lung cancer group and 10 subjects in the normal control group. Accordingly, 575 and 404 -glycosites were revealed for the lung cancer group and normal control group. In particular, 154 -glycosites and 259 site-specific glycoforms were significantly dysregulated in the lung cancer group. Several -glycosites located at the same glycoprotein and glycans attached to the same -glycosites were observed with differential expressions, including haptoglobin, Mucin-5B, lactotransferrin, and α-1-acid glycoprotein 1. These -glycoproteins were mainly related to inflammatory responses, infectious diseases, and cancers. Our study achieved comprehensive characterization of salivary -glycoproteome, and dysregulated site-specific glycoforms hold promise for noninvasive detection of lung cancer.
异常的蛋白质糖基化是癌症的一个标志，具有很大的癌症检测潜力。然而，由于其高度异质性、复杂性和低丰度，对糖基化进行大规模和深入的分析仍然具有挑战性。人唾液是一种有吸引力的诊断体液，但很少有研究探索其用于肺癌的糖蛋白组。在这里，我们利用基于两性离子亲水性相互作用色谱的策略来特异性富集唾液糖肽。通过定量蛋白质组学分析，从非小细胞肺癌组 10 名受试者和正常对照组 10 名受试者的混合唾液样本中，分别鉴定出 1492 个和 1234 个完整的糖肽。相应地，为肺癌组和正常对照组分别揭示了 575 个和 404 个糖基化位点。特别是，在肺癌组中，有 154 个糖基化位点和 259 个特定糖型被显著失调。几个位于同一糖蛋白上的糖基化位点和连接到同一糖基化位点上的糖链被观察到差异表达，包括触珠蛋白、Mucin-5B、乳铁传递蛋白和α-1-酸性糖蛋白 1。这些糖蛋白主要与炎症反应、传染病和癌症有关。我们的研究实现了唾液糖蛋白组的全面表征，失调的特定糖型有望用于非侵入性检测肺癌。
