肝癌发生过程中的血清糖蛋白凝集素亲和谱比较  

Serum glycoproteome profiling by lecfin affinity microarray to distinguish the various stages of primary liver carcinogenesis

作　　者：景瑞[1] 胡衡[3] 孙淳[2] 黄天壬[1] 邓伟[1] 利基林 余家华[1] 刘银坤[2] 张春燕[1] 

机构地区：[1]广西医科大学附属肿瘤医院,530021 [2]复旦大学附属中山医院肝癌研究所 [3]复旦大学上海医学院

出　　处：《中华肝脏病杂志》2014年第5期358-363,共6页Chinese Journal of Hepatology

基　　金：国家自然科学基金（81060173）,广西自然科学基金（2010GXNSFA013242）,广西医疗卫生重点科研项目（重2010117）

摘　　要：目的应用凝集素亲和技术寻找肝癌高危人群进展为肝癌过程中的特征性血清糖蛋白凝集素亲和谱，并探讨其生物学意义。方法对广西肝癌高发区肝癌高危队列定期进行复查随访，将队列中陆续新发的肝癌、肝硬化、肝炎患者分别组成肝癌组、肝硬化组、肝炎组，并匹配正常对照组，应用凝集素芯片技术，比较肝癌组、肝硬化组、肝炎组及正常对照组的血清糖蛋白凝集素亲和谱，并用Westemblot方法对有意义的差异性糖蛋白进行验证。采用独立样本t检验对组间亲和信号强度进行比较。结果在肝癌的发生过程中，血清糖蛋白表现出对橙黄网胞盘菌凝集素、尾穗苋凝集素（ACL）、伴刀豆凝集素（ConA）、小扁豆凝集素（LCA）、桑橙凝集素、槲寄生凝集素、红腰果E型凝集素（PHA—E）、红腰果L型凝集素（PHA—L）、豌豆凝集素（PSA）、蓖麻凝集素（RCA—I）、西泽接骨木凝集素（SNA）、马铃薯凝集素（STL）、槲寄生凝集素（VAL）和麦胚凝集素（WGA）14种凝集素的亲和信号增强（P〈0．05），提示在肝癌的发生过程中，患者血清里可能存在增多的岩藻糖、N-乙酰葡糖胺、N-乙酰半乳糖胺、甘露糖、平分型GlcNAc、末端β1-4链接半乳糖等结构。将肝癌组的亲和信号增强与其他各组比较，除SNA在肝癌组与肝炎组的亲和信号强度差异无统计学意义（P〉0．05）外，其他凝集素的肝癌组与其他组比较，差异均有统计学意义（P值均〈0．05）。结论广西肝癌高危人群从HBsAg阳性、肝炎、肝硬化，直至进展为肝癌的过程中，血清糖蛋白聚糖的变化具有特征性的差异，提示其与肝癌的发生和发展密切相关，为寻找肝癌早期诊断相关的糖标志物提供了重要参考。Objective To identify specific serum glycoproteome profiles that correspond to the carcinogenic process of primary liver cancer （PLC） by analyzing a population with high-incidence of PLC using lectin affinity microarray. Methods Serum samples were collected from individuals classified as high- risk for PLC （including patients with liver cirrhosis and hepatitis B） and development of PLC was recorded. Healthy individuals served as normal controls. The serum samples were subjected to glycoproteome profling by using lectin microarrays and the results were confirmed by lectin blot. Between-group differences were statistically analyzed. ResuRs PLC carcinogenesis was found to be correlated with enhanced affinity for AAL, ACL, ConA, LCA, MPL, NML, PHA-E, PHA-L, PSA, RCA-I, STL, VAL, WGA, and SNA （P 〈 0.05）. These data implied that changes in specific glycan structures, such as ctFuc, GlcNAc, GalNAc, mannose, bisecting GlcNAc and terminal 131-4 Gal, may be involved in PLC carcinogenesis. The PLC group showed significantly different results for all detected lectins, except SNA （P 〈 0.05）. However, among the PLC group, the SNA affinity was not significantly different for the hepatitis B group （P = 0.443, P 〉 0.05）. Conclusion Glycans may be associated with the carcinogenic process of PLC and may be developed as diagnostic and prognostic biomarkers of PLC in the future.

关 键 词：外源凝集素类 芯片分析技术 聚糖 

分 类 号：R735.7[医药卫生—肿瘤]