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犬类肝脏疾病中微小RNA - 122的敏感性和特异性

Sensitivity and specificity of microRNA-122 for liver disease in dogs.

作者信息

Oosthuyzen W, Ten Berg P W L, Francis B, Campbell S, Macklin V, Milne E, Gow A G, Fisher C, Mellanby R J, Dear J W

机构信息

Pharmacology, Toxicology and Therapeutics, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, The United Kingdom.

Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool, The United Kingdom.

出版信息

J Vet Intern Med. 2018 Sep;32(5):1637-1644. doi: 10.1111/jvim.15250. Epub 2018 Aug 2.

Abstract

BACKGROUND

Current tests for diagnosing liver disease in dogs are sub-optimal. MicroRNA-122 (miR-122) is a sensitive and specific biomarker of liver injury in humans and rodents. Circulating miR-122 could have utility in identifying dogs with liver disease.

OBJECTIVE

Establish the reference interval for miR-122 in healthy dogs and determine performance in a range of dog breeds with liver disease and control animals with non-liver disease.

ANIMALS

Stored serum from 120 healthy dogs, 100 dogs with non-liver diseases, and 30 dogs with histologically confirmed liver disease was analyzed.

METHODS

Retrospective study. Medical records of dogs with liver disease, non-liver disease and healthy dogs were reviewed. Serum miR-122 concentrations were measured by PCR and compared with the characteristics of the dogs and their conventional clinical measurements.

RESULTS

In healthy dogs the 2.5th, 50th, and 97.5th quartiles of miR-122 were 110 (90% CI 80-114), 594 (505-682), and 3312 (2925-5144) copies/μL, respectively. There was no difference between healthy dogs and dogs with non-liver disease (median ± IQR: healthy dogs 609 [327-1014] copies/μL; non-liver disease 607 [300-1351] copies/μL). miR-122 was higher in dogs with liver disease (11 332 [4418-20 520] copies/μL, P < .001 compared to healthy dogs). miR-122 identified dogs with liver disease with high accuracy (receiver operating characteristic area under curve for comparison with healthy dogs: 0.93 [95% CI 0.86-0.99]). The upper limit of normal for healthy dogs (3312 copies/μL) had a sensitivity of 77% and specificity of 97% for identifying liver disease.

CONCLUSION AND CLINICAL IMPORTANCE

Liver disease can be sensitively and specifically diagnosed in dogs by measurement of miR-122.

摘要

背景

目前用于诊断犬类肝脏疾病的检测方法并不理想。微小RNA-122(miR-122)是人类和啮齿动物肝脏损伤的一种敏感且特异的生物标志物。循环miR-122可能有助于识别患有肝脏疾病的犬类。

目的

确定健康犬类中miR-122的参考区间,并评估其在一系列患有肝脏疾病的犬种以及非肝脏疾病对照动物中的表现。

动物

分析了120只健康犬、100只非肝脏疾病犬和30只经组织学确诊为肝脏疾病的犬的储存血清。

方法

回顾性研究。查阅了患有肝脏疾病、非肝脏疾病的犬以及健康犬的病历。通过聚合酶链反应(PCR)测量血清miR-122浓度,并与犬的特征及其传统临床测量结果进行比较。

结果

在健康犬中,miR-122的第2.5百分位数、第50百分位数和第97.5百分位数分别为110(90%置信区间80 - 114)、594(505 - 682)和3312(2925 - 5144)拷贝/微升。健康犬与非肝脏疾病犬之间无差异(中位数±四分位间距:健康犬609 [327 - 1014]拷贝/微升;非肝脏疾病犬607 [300 - 1351]拷贝/微升)。患有肝脏疾病的犬的miR-122水平更高(11332 [4418 - 20520]拷贝/微升,与健康犬相比P <.001)。miR-122能高精度地识别患有肝脏疾病的犬(与健康犬比较的受试者工作特征曲线下面积:0.93 [95%置信区间0.86 - 0.99])。健康犬的正常上限(3312拷贝/微升)在识别肝脏疾病时的敏感性为77%,特异性为97%。

结论及临床意义

通过测量miR-122可敏感且特异地诊断犬类肝脏疾病。

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