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Identification of abnormal fucosylated-glycans recognized by LTL in saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma
Glycobiology ( IF 4.3 ) Pub Date : 2019-01-07 , DOI: 10.1093/glycob/cwy108
Jiaxu Zhang 1 , Yaogang Zhong 1 , Peixin Zhang 2 , Haoqi Du 1 , Jian Shu 1 , Xiawei Liu 1 , Hua Zhang 3 , Yonghong Guo 4 , Zhansheng Jia 2 , Lili Niu 5 , Fuquan Yang 5 , Zheng Li 1
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The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide. There is evidence to display the alterations of salivary N-linked glycans related to the development of HBV-infected liver diseases. Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS. The results showed that the expression level of fucosylated glycans recognized by LTL was significantly increased in HCC compared with other subjects (P < 0.0001). Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates. Then, N/O- glycans were released from the isolated glycoproteins with PNGase F and NaClO, and were identified by MALDI-TOF-MS, respectively. Totally, there were 21/20, 25/18, 29/19, and 28/24 N/O-glycan peaks that were identified and annotated with proposed structures in saliva of HV, HB, HC, and HCC. Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases. One N-glycan peak (m/z 2205.766) was unique in HC, and 9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402) were unique in HCC. This study could facilitate the discovery of biomarkers for HC and HCC based on precise alterations of fucosylated N/O-glycans in saliva.

中文翻译:

LTL识别的乙型肝炎病毒引起的慢性肝炎,肝硬化和肝细胞癌唾液中异常岩藻糖基化聚糖的鉴定

乙型肝炎病毒(HBV)引起的慢性肝病是全球范围内严重的健康威胁。有证据显示唾液N链聚糖的变化与HBV感染的肝脏疾病的发展有关。在这里,我们进一步调查了120名受试者(30名健康志愿者(HV),30名乙肝患者(HB),30名肝硬化患者(HC)和30名受试者)的唾液中LTL识别的岩藻糖基化N / O聚糖的变化唾液微管和MALDI-TOF / TOF-MS检测肝细胞癌(HCC)的患者。结果表明,与其他受试者相比,LTL识别的肝癌中岩藻糖基化聚糖的表达水平显着增加(P<0.0001)。此外,通过LTL-磁性颗粒结合物从合并的HV,HB,HC和HCC唾液中分离出岩藻糖基化糖蛋白。然后,用PNGase F和NaClO从分离的糖蛋白中释放N / O-聚糖,并分别通过MALDI-TOF-MS进行鉴定。总共,在HV,HB,HC和HCC的唾液中鉴定并注释了21 / 20、25 / 18、29 / 19和28/24 N / O聚糖峰,并提出了相应的结构注释。在总数中,有8个N-聚糖峰(例如m / z 1905.634、2158.777和2905.036)和15 O-聚糖峰(例如1177.407、1308.444和1322.444)仅出现在HBV诱发的肝病患者中。在HC中,一个N-聚糖峰(m / z 2205.766)是唯一的,在HCC中有9个O-聚糖峰(例如m / z 1157.420、1163.417和1193.402)是唯一的。这项研究可以基于唾液中岩藻糖基化N / O-聚糖的精确变化,促进HC和HCC生物标记物的发现。
更新日期:2019-01-07
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