中国循证儿科杂志 ›› 2018, Vol. 13 ›› Issue (5): 343-347.

• 论著 • 上一篇    下一篇

基于高通量检测发现并验证胆道闭锁血清标志物

郑超1,聂雅娟1,董瑞2,余发星1,郑珊1   

  1. 1. 复旦大学附属儿科医院
    2. 复旦大学儿科医院
  • 收稿日期:2018-06-27 修回日期:2018-12-01 出版日期:2018-10-25 发布日期:2018-10-25
  • 通讯作者: 聂雅娟

Screening and validation for serological factors involved in the progression of biliary atresia based on high-throughput antibody array

  • Received:2018-06-27 Revised:2018-12-01 Online:2018-10-25 Published:2018-10-25

摘要: 目的:探讨与胆道闭锁发病机制相关的血清分子标志物。 方法:收集复旦大学附属儿科医院收治的胆道闭锁患儿与胆总管囊肿患儿的血清,利用高通量抗体芯片技术检测血清中细胞因子水平,采用GSH-CAA-X00进行数据分析。根据抗体芯片检测结果,通过复习文献选取部分分子标志物采用ELISA法进行扩大样本验证。 结果:胆道闭锁患儿5例,胆总管囊肿患儿3例。47/1 002个蛋白在两组表达差异有统计学意义(P均<0.05),且两者倍数相差在1.2倍以上,在胆道闭锁患儿血清中表达上调34个,下调13个。选取IL-6、IL-8和IL-10指标在50例胆道闭锁患儿和30例胆总管囊肿患儿中采用ELISA法进行验证,结果显示IL-6、IL-8和IL-10在胆道闭锁患儿血清中浓度均高于胆总管囊肿患儿。 结论:利用血清抗体芯片分析技术,能够对血清样本中的多种蛋白进行高通量化地检测分析,并筛选出部分具有临床诊断价值的胆道闭锁血清标记蛋白,为进一步探索胆道闭锁发病机制以及诊断策略奠定新的研究基础。

关键词: Antibody array, Biliary atresia, Biomarker, 胆道闭锁, 抗体芯片, 生物标志物

Abstract: Objective:To identify serological factors involved in disease pathogenesis in biliary atresia (BA) patients. Methods:In this study, we collected serum of the patients with BA or choledochal cyst diagnosed by cholangiography and postoperative pathology without extrahepatic malformation hospitalized in Children's Hospital of Fudan University, and screened differentially expressed serological factors in BA patients using a high-throughput antibody array technology. GSH-CAA-X00 software was used to analyze the data. More serum samples were collected from patients with BA or choledochal cyst to be further verified by ELISA. Results:Eight patients including 5 cases with BA and 3 cases with choledochal cyst were recruited. A total of 1 002 serum factors were analyzed simultaneously using high-throughput antibody array approach, among which 47 serum factors expressed differentially between two groups with 34 factors being up-regulated and 13 factors being down-regulated in BA patients (P<0.05). The higher expression of IL-6, IL-8 and IL-10 were confirmed in another 50 patients with BA than that of 30 patients with choledochal cyst. Conclusion:We demonstrated the feasibility of high-throughput screen of serological factors related to BA, and several newly discovered factors might be further characterized and used as diagnostic or prognostic indicators for BA.

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