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Chinese Medical Sciences Journal ›› 2019, Vol. 34 ›› Issue (3): 157-167.doi: 10.24920/003504

• 论著 •    下一篇

中国不同地区健康人尿液蛋白质组的地域差异

吴建强1,2,秦伟伟3,潘利4,王小蓉2,张彪4,单广良4,*(),高友鹤3,*()   

  1. 1 中国医学科学院北京协和医院医学科学研究中心,中国医学科学院 北京协和医学院,北京 100730
    2 中国医学科学院基础医学研究所病理生理学系,中国医学科学院 北京协和医学院,北京 100005
    3 北京师范大学生命科学学院生物化学与分子生物学系,基因工程药物与生物技术北京重点实验室,北京 100875
    4 流行病与卫生统计学系,中国医学科学院 北京协和医学院,北京 100005
  • 收稿日期:2019-04-22 出版日期:2019-09-30 发布日期:2019-04-22
  • 通讯作者: 单广良,高友鹤 E-mail:guangliang_shan@163.com;gaoyouhe@bnu.edu.cn

Regional Differences of the Urinary Proteomes in Healthy Chinese Individuals

Wu Jianqiang1,2,Qin Weiwei3,Pan Li4,Wang Xiaorong2,Zhang Biao4,Shan Guangliang4,*(),Gao Youhe3,*()   

  1. 1 Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China;2 Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China; 3 Department of Biochemistry and Molecular Biology, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing Normal University, Beijing 100875, China; 4 Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China;
  • Received:2019-04-22 Published:2019-09-30 Online:2019-04-22
  • Contact: Shan Guangliang,Gao Youhe E-mail:guangliang_shan@163.com;gaoyouhe@bnu.edu.cn

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摘要：

目的 尿液是临床蛋白质组学研究的理想生物标志物来源。在多中心的临床研究中,研究对象存在地域性的生理差异很常见,本研究的目的是分析不同地区健康个体的尿液蛋白质组是否存在差异。

方法 本研究收集了中国海口、西安和西宁三个城市健康城市居民的尿液样本,并采用基于尿膜（Urimem）的方法保存尿液蛋白。使用液相色谱串联高分辨质谱分析比较了其中27名健康成人尿液样品的蛋白质组。

结果 基于label-free蛋白质组定量,我们从Urimem样品中共鉴定出1898种尿液蛋白,其中56个尿液蛋白在不同地区健康个体中差异表达。分层聚类分析显示:尿液蛋白质组的地域差异小于性别差异。对性别进行分层后,在男性样品中鉴定到17个差异蛋白,在女性样品中鉴定到93个差异蛋白。其中有些差异蛋白在既往临床研究中曾被作为疾病生物标志物。

结论 Urimem可以用于大规模尿液样品的蛋白保存,从而加速生物样本库的发展及尿液蛋白组疾病生物标志物的研究。地域差异是影响正常尿液蛋白质组的混杂因素,在未来基于人群的多中心的疾病标志物研究中应予以考虑。

关键词: 尿液, 蛋白质组学, 生物样本库, 生物标志物, 地域差异

Abstract:

Objective Urine is a promising biomarker source for clinical proteomics studies. Regional physiological differences are common in multi-center clinical studies. In this study, we investigate whether significant differences are present in the urinary proteomes of individuals from different regions in China.

Methods In this study, morning urine samples were collected from healthy urban residents in three regions of China (Haikou, Xi’an and Xining) and urinary proteins were preserved using a membrane-based method (Urimem). The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among three regions. Functional annotation of the differential proteins among the three areas was analyzed using the DAVID online database, and pathway enrichment of the differential urinary proteins was analyzed using KEGG.

Results We identified 1898 proteins from Urimem samples using label-free proteome quantification, of which 56 urine proteins were differentially expressed among the three regions (P < 0.05). Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than inter-sex differences. After gender stratification, 16 differential proteins were identified in male samples and 84 differential proteins were identified in female samples. Among these differential proteins, several proteins have been previously reported as urinary disease biomarkers.

Conclusions Urimem will facilitate urinary protein storage for large-scale urine sample collection. Regional differences are a confounding factor influencing the urine proteome and should be considered in future multi-center biomarker studies.

Key words: urine, proteomics, biobank, biomarkers, regional differences