Åström Eva, Stål Per, Zenlander Robin, Edenvik Pia, Alexandersson Catharina, Haglund Mats, Rydén Ingvar, Påhlsson Peter
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Medicine, Division of Gastroenterology and Hepatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
PLoS One. 2017 Mar 15;12(3):e0173897. doi: 10.1371/journal.pone.0173897. eCollection 2017.
Altered fucosylation of glycoproteins is associated with development of hepatocellular carcinoma (HCC). Lectins have been commonly used to assay changes in fucosylation of plasma glycoproteins. In the present study a recombinantly engineered form of the fucose binding lectin Aleuria aurantia (AAL) consisting of a single binding site for fucose (S2), was used to construct a reverse lectin ELISA method. Microtiter plates coated with the S2 lectin were used to capture glycoproteins from plasma samples followed by antibody detection of S2-bound fucosylated α1-acid glycoprotein (S2-bound AGP). The method was used to compare the level of S2-bound AGP in serum samples from a small cohort of patients with hepatitis, cirrhosis or HCC. Using the reverse S2 lectin ELISA it was shown that the levels of S2-bound AGP was significantly higher in HCC patients compared to non-cancer patients and that there was also a significant elevation of S2-bound AGP in HCC patients compared to cirrhosis patients. There was no correlation between the level of S2-bound AGP and total AGP concentration. The performance of S2-bound AGP in differentiating HCC from cirrhosis samples or hepatitis samples were compared to other markers. A combination of S2-bound AGP, α-fetoprotein and AGP concentration showed performances giving area under receiver operating curves of 0.87 and 0.95 respectively.
糖蛋白岩藻糖基化改变与肝细胞癌（HCC）的发生发展相关。凝集素常用于检测血浆糖蛋白岩藻糖基化的变化。在本研究中，一种由单个岩藻糖结合位点（S2）组成的重组工程化岩藻糖结合凝集素橙黄网柄牛肝菌（AAL），被用于构建反向凝集素酶联免疫吸附测定法。用包被有S2凝集素的微量滴定板从血浆样本中捕获糖蛋白，随后通过抗体检测与S2结合的岩藻糖基化α1-酸性糖蛋白（S2结合的AGP）。该方法用于比较一小群肝炎、肝硬化或HCC患者血清样本中S2结合的AGP水平。使用反向S2凝集素酶联免疫吸附测定法表明，与非癌症患者相比，HCC患者中S2结合的AGP水平显著更高，并且与肝硬化患者相比HCC患者中S2结合的AGP也有显著升高。S2结合的AGP水平与总AGP浓度之间无相关性。将S2结合的AGP在区分HCC与肝硬化样本或肝炎样本中的性能与其他标志物进行了比较。S2结合的AGP、甲胎蛋白和AGP浓度的组合显示，其性能分别给出了受试者工作曲线下面积为0.87和0.95。
