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一个由患有各种肾脏疾病和前列腺癌的患者生成的综合尿液蛋白质组数据库。

A Comprehensive Urine Proteome Database Generated From Patients With Various Renal Conditions and Prostate Cancer.

作者信息

Swensen Adam C, He Jingtang, Fang Alexander C, Ye Yinyin, Nicora Carrie D, Shi Tujin, Liu Alvin Y, Sigdel Tara K, Sarwal Minnie M, Qian Wei-Jun

机构信息

Integrative Omics, Pacific Northwest National Laboratory, Biological Sciences Division, Richland, WA, United States.

Department of Urology, University of Washington, Seattle, WA, United States.

出版信息

Front Med (Lausanne). 2021 Apr 13;8:548212. doi: 10.3389/fmed.2021.548212. eCollection 2021.

Abstract

Urine proteins can serve as viable biomarkers for diagnosing and monitoring various diseases. A comprehensive urine proteome database, generated from a variety of urine samples with different disease conditions, can serve as a reference resource for facilitating discovery of potential urine protein biomarkers. Herein, we present a urine proteome database generated from multiple datasets using 2D LC-MS/MS proteome profiling of urine samples from healthy individuals (HI), renal transplant patients with acute rejection (AR) and stable graft (STA), patients with non-specific proteinuria (NS), and patients with prostate cancer (PC). A total of ~28,000 unique peptides spanning ~2,200 unique proteins were identified with a false discovery rate of <0.5% at the protein level. Over one third of the annotated proteins were plasma membrane proteins and another one third were extracellular proteins according to gene ontology analysis. Ingenuity Pathway Analysis of these proteins revealed 349 potential biomarkers in the literature-curated database. Forty-three percentage of all known cluster of differentiation (CD) proteins were identified in the various human urine samples. Interestingly, following comparisons with five recently published urine proteome profiling studies, which applied similar approaches, there are still ~400 proteins which are unique to this current study. These may represent potential disease-associated proteins. Among them, several proteins such as serpin B3, renin receptor, and periostin have been reported as pathological markers for renal failure and prostate cancer, respectively. Taken together, our data should provide valuable information for future discovery and validation studies of urine protein biomarkers for various diseases.

摘要

尿液蛋白质可作为诊断和监测各种疾病的可行生物标志物。一个由各种不同疾病状况的尿液样本生成的综合尿液蛋白质组数据库,可作为促进发现潜在尿液蛋白质生物标志物的参考资源。在此,我们展示了一个尿液蛋白质组数据库,该数据库是通过对来自健康个体(HI)、急性排斥反应的肾移植患者(AR)和移植稳定患者(STA)、非特异性蛋白尿患者(NS)以及前列腺癌患者(PC)的尿液样本进行二维液相色谱-串联质谱(2D LC-MS/MS)蛋白质组分析,从多个数据集中生成的。在蛋白质水平上,共鉴定出约28,000个独特肽段,涵盖约2,200个独特蛋白质,错误发现率<0.5%。根据基因本体分析,超过三分之一的注释蛋白质是质膜蛋白,另外三分之一是细胞外蛋白。对这些蛋白质进行的 Ingenuity 通路分析在文献整理数据库中揭示了349个潜在生物标志物。在各种人类尿液样本中鉴定出了所有已知分化簇(CD)蛋白的43%。有趣的是,与最近发表的五项采用类似方法的尿液蛋白质组分析研究进行比较后,仍有大约400种蛋白质是本研究独有的。这些可能代表潜在的疾病相关蛋白。其中,诸如丝氨酸蛋白酶抑制剂B3、肾素受体和骨膜蛋白等几种蛋白质分别被报道为肾衰竭和前列腺癌的病理标志物。综上所述,我们的数据应为未来各种疾病尿液蛋白质生物标志物的发现和验证研究提供有价值的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b705/8076675/79be7ef8fd22/fmed-08-548212-g0001.jpg

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