Department of Laboratory Medicine, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China.
Int J Cancer. 2010 Jul 1;127(1):148-59. doi: 10.1002/ijc.25030.
The early diagnosis of hepatocellular carcinoma (HCC) is of great clinical desirable due to lack of specific and sensitive markers. Alterations in the sugar chains of glycoprotein synthesized by the liver contribute to the molecular basis of abnormalities in carcinogenesis. This study aims to construct and assess the diagnostic value of N-glycan based diagnostic model in HCC identification and follow-up. A total of 393 subjects including HBV-related HCC, liver fibrosis and healthy controls were recruited. Follow-up was carried out before and after surgical treatment in HCC. N-glycome of serum glycoprotein was profiled by DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Multiparameters diagnostic models were constructed based on N-glycan markers. The result found that 2 N-glycan structure abundances (NG1A2F, Peak 4; NA3Fb, Peak 9) were useful as N-glycan markers. The diagnostic efficacy of the log ratio [log(p9/4)] was similar to that of AFP in differentiating HCC from fibrosis. The accuracy and sensitivity of the diagnostic model combining AFP and N-glycan markers (Cscore B) were increased 7-10% compared with that of AFP. Log(p9/4) was more efficient in monitoring the progression of HCC with regarding to vascular invasion at improved specificity (16%) and accuracy (8%) compared with that of AFP. The N-glycan markers were found to be changed significantly after surgical resection in HCC follow-up. We conclude that the branching alpha (1,3)-fucosylated triantennary glycan and a biantennary glycan are promising as N-glycan markers. The diagnostic models based on the N-glycan markers and AFP improve the efficacy in HCC diagnosis and progression monitoring.
肝细胞癌 (HCC) 的早期诊断具有重要的临床意义，因为缺乏特异性和敏感的标志物。肝脏合成的糖蛋白的糖链改变是导致癌变过程中异常的分子基础。本研究旨在构建和评估基于 N-糖基的诊断模型在 HCC 识别和随访中的诊断价值。共招募了 393 名受试者，包括 HBV 相关 HCC、肝纤维化和健康对照者。在 HCC 手术治疗前后进行了随访。采用 DNA 测序仪辅助荧光辅助糖电泳 (DSA-FACE) 对血清糖蛋白的 N-聚糖组进行了分析。基于 N-糖基标志物构建了多参数诊断模型。结果发现，2 种 N-糖链结构丰度 (NG1A2F，峰 4；NA3Fb，峰 9) 可用作 N-糖基标志物。log(p9/4) 的诊断效能与 AFP 区分 HCC 与纤维化相似。与 AFP 相比，联合 AFP 和 N-糖基标志物 (Cscore B) 的诊断模型的准确性和敏感性提高了 7-10%。与 AFP 相比，log(p9/4) 在监测 HCC 进展方面更有效，特异性提高了 16%，准确性提高了 8%，特别是在血管侵犯方面。在 HCC 随访中，发现 N-糖基标志物在手术后明显改变。我们得出结论，分支的α(1,3)-岩藻糖基三触角聚糖和双触角聚糖是有前途的 N-糖基标志物。基于 N-糖基标志物和 AFP 的诊断模型提高了 HCC 诊断和进展监测的疗效。
