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犬骨关节炎N-聚糖生物标志物的发现

Discovery of N-glycan Biomarkers for the Canine Osteoarthritis.

作者信息

Lee Hyunjun, Lee Ahyun, Seo Nari, Oh Jiwon, Kweon Oh-Kyeong, An Hyun Joo, Kim Jaehan

机构信息

Department of Food and Nutrition, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea.

Graduate School of Analytical Science and Technology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea.

出版信息

Life (Basel). 2020 Sep 14;10(9):199. doi: 10.3390/life10090199.

DOI:10.3390/life10090199
PMID:32937769
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7555374/
Abstract

Protein glycosylation is a post-translational modification that impacts on protein activity, stability, and interactions. It was sensitively altered by the cellular state and, therefore, is now used for a diagnostic or prognostic indicator of various human diseases such as cancer. To evaluate the clinical feasibility in the veterinary area, the N-glycan biomarkers were discovered from canine serum for the diagnosis of osteoarthritis (OA), which is one of the most common diseases of dogs. N-glycome was obtained from 20 μL of canine serum by the enzymatic cleavage followed by the purification and enrichment using solid-phase extraction. Independent compositions of 163 and 463 N-glycans were found from healthy control (n = 41) and osteoarthritis patients (n = 92), respectively. Initially, 31 of the potential biomarkers were screened by the -values below 1.0 × 10 from ANOVA. Then, the area under the curve (AUC) and the intensity ratio between OA patient and healthy control (P/C ratio) were calculated. Considering the diagnostic efficacy, the AUC bigger than 0.9 and the P/C ratio larger than 3.0 were used to discover 16 N-glycans as diagnostic biomarkers. Particularly, five of the diagnostic biomarkers were AUC above 0.99 and three of N-glycans had AUC 1.0. The results suggest a clear possibility for N-glycan biomarkers to be used as a clinical tool in the veterinary medical area enabling to provide objective and non-invasive diagnostic information.

摘要

蛋白质糖基化是一种翻译后修饰,会影响蛋白质的活性、稳定性和相互作用。它会随细胞状态而发生敏感变化,因此现在被用作多种人类疾病(如癌症)的诊断或预后指标。为了评估在兽医领域的临床可行性,从犬血清中发现了用于诊断骨关节炎(OA)的N-聚糖生物标志物,OA是犬类最常见的疾病之一。通过酶切从20μL犬血清中获得N-糖组,然后使用固相萃取进行纯化和富集。在健康对照(n = 41)和骨关节炎患者(n = 92)中分别发现了163种和463种独立组成的N-聚糖。最初,通过方差分析筛选出31种潜在生物标志物,其P值低于1.0×10。然后,计算曲线下面积(AUC)以及OA患者与健康对照之间的强度比(P/C比)。考虑到诊断效力,将AUC大于0.9且P/C比大于3.0作为标准,发现了16种N-聚糖作为诊断生物标志物。特别地,其中5种诊断生物标志物的AUC高于0.99,3种N-聚糖的AUC为1.0。结果表明,N-聚糖生物标志物有很大可能性作为兽医医学领域的临床工具,能够提供客观且非侵入性的诊断信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5f/7555374/2343267a3c83/life-10-00199-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5f/7555374/a9079de00903/life-10-00199-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5f/7555374/2343267a3c83/life-10-00199-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5f/7555374/a9079de00903/life-10-00199-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5f/7555374/2343267a3c83/life-10-00199-g002a.jpg

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本文引用的文献

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Comprehensive Characterization of Biotherapeutics by Selective Capturing of Highly Acidic Glycans Using Stepwise PGC-SPE and LC/MS/MS.采用分步 PGC-SPE 和 LC/MS/MS 选择性捕获高度酸性糖来全面表征生物治疗药物。
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Profiling of different pancreatic cancer cells used as models for metastatic behaviour shows large variation in their N-glycosylation.
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