Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul 03080, Korea.
Department of Biomedical Engineering, Seoul National University College of Engineering, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
J Proteome Res. 2022 Jun 3;21(6):1548-1557. doi: 10.1021/acs.jproteome.2c00196. Epub 2022 May 10.
Glycoproteins have many important biological functions. In particular, aberrant glycosylation has been observed in various cancers, such as liver cancer. A well-known glycoprotein biomarker is α-fetoprotein (AFP), a surveillance biomarker for hepatocellular carcinoma (HCC) that contains a glycosylation site at asparagine 251. The low diagnostic sensitivity of AFP led researchers to focus on AFP-L3, which has the same sequence as conventional AFP but contains a fucosylated glycan. AFP-L3 has high affinity for (LCA) lectin, prompting many groups to use it for detecting AFP-L3. However, a few studies have identified more effective lectins for fractionating AFP-L3. In this study, we compared the amounts of enriched AFP-L3 with five fucose-specific lectins─LCA, (LTL), (UEA I), (AAL), and (AOL)─to identify better lectins and improve HCC diagnostic assays using mass spectrometry (MS). Our results indicate that LTL was the most effective lectin for capturing AFP-L3 species, yielding approximately 3-fold more AFP-L3 than LCA from the same pool of HCC serum samples. Thus, we recommend the use of LTL for AFP-L3 assays, given its potential to improve the diagnostic sensitivity in patients having limited results by conventional LCA assay. The MS data have been deposited to the PeptideAtlas (PASS01752).
糖蛋白具有许多重要的生物学功能。特别是，各种癌症中都观察到了异常的糖基化，例如肝癌。一种著名的糖蛋白生物标志物是甲胎蛋白（AFP），它是肝细胞癌（HCC）的监测生物标志物，在天冬酰胺 251 位含有一个糖基化位点。AFP 的低诊断灵敏度促使研究人员关注 AFP-L3，它与常规 AFP 具有相同的序列，但含有一个岩藻糖基化的聚糖。AFP-L3 与 （LCA）凝集素具有高亲和力，促使许多研究小组使用它来检测 AFP-L3。然而，一些研究已经确定了更有效的用于分离 AFP-L3 的凝集素。在这项研究中，我们比较了五种岩藻糖特异性凝集素（LCA、LTL、UEA I、AAL 和 AOL）富集 AFP-L3 的量，以确定更好的凝集素，并使用质谱法（MS）改进 HCC 诊断检测。我们的结果表明，LTL 是捕获 AFP-L3 物种最有效的凝集素，从相同的 HCC 血清样本池中捕获的 AFP-L3 比 LCA 多约 3 倍。因此，鉴于其有可能提高传统 LCA 检测结果有限的患者的诊断灵敏度，我们建议使用 LTL 进行 AFP-L3 检测。MS 数据已被存入 PeptideAtlas（PASS01752）。
