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用于检测包裹性腹膜硬化的腹腔引流液微小RNA谱

Peritoneal effluent MicroRNA profile for detection of encapsulating peritoneal sclerosis.

作者信息

Wu Kun-Lin, Chou Che-Yi, Chang Hui-Yin, Wu Chih-Hsun, Li An-Lun, Chen Chien-Lung, Tsai Jen-Chieh, Chen Yi-Fan, Chen Chiung-Tong, Tseng Chin-Chung, Chen Jin-Bor, Wang I-Kuan, Hsu Yu-Juei, Lin Shih-Hua, Huang Chiu-Ching, Ma Nianhan

机构信息

Department of Biomedical Sciences and Engineering, Institute of Systems Biology and Bioinformatics, National Central University, Taoyuan, Taiwan; Division of Nephrology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Division of Nephrology, Department of Internal Medicine, Asia University Hospital, Taichung, Taiwan.

出版信息

Clin Chim Acta. 2022 Nov 1;536:45-55. doi: 10.1016/j.cca.2022.09.007. Epub 2022 Sep 18.

Abstract

BACKGROUND

Encapsulating peritoneal sclerosis (EPS) is a catastrophic complication of peritoneal dialysis (PD) with high mortality. Our aim is to develop a novel noninvasive microRNA (miRNA) test for EPS.

METHODS

We collected 142 PD effluents (EPS: 62 and non-EPS:80). MiRNA profiles of PD effluents were examined by a high-throughput real-time polymerase chain reaction (PCR) array to first screen. Candidate miRNAs were verified by single real-time PCR. The model for EPS prediction was evaluated by multiple logistic regression and machine learning.

RESULTS

Seven candidate miRNAs were identified from the screening of PCR-array of 377 miRNAs. The top five area under the curve (AUC) values with 5 miRNA-ratios were selected using 127 samples (EPS: 56 vs non-EPS: 71) to produce a receiver operating characteristic curve. After considering clinical characteristics and 5 miRNA-ratios, the accuracies of the machine learning model of Random Forest and multiple logistic regression were boosted to AUC 0.97 and 0.99, respectively. Furthermore, the pathway analysis of miRNA associated targeting genes and miRNA-compound interaction network revealed that these five miRNAs played the roles in TGF-β signaling pathway.

CONCLUSION

The model-based miRNA expressions in PD effluents may help determine the probability of EPS and provide further therapeutic opinion for EPS.

摘要

背景

包裹性腹膜硬化(EPS)是腹膜透析(PD)的一种灾难性并发症,死亡率很高。我们的目标是开发一种用于EPS的新型非侵入性微小RNA(miRNA)检测方法。

方法

我们收集了142份PD流出液(EPS:62份,非EPS:80份)。通过高通量实时聚合酶链反应(PCR)阵列检测PD流出液的miRNA谱以进行初步筛选。候选miRNA通过单重实时PCR进行验证。通过多元逻辑回归和机器学习评估EPS预测模型。

结果

从377个miRNA的PCR阵列筛选中鉴定出7个候选miRNA。使用127个样本(EPS:56份,非EPS:71份)选择了5个miRNA比率的前五个曲线下面积(AUC)值,以生成受试者工作特征曲线。在考虑临床特征和5个miRNA比率后,随机森林机器学习模型和多元逻辑回归的准确率分别提高到AUC 0.97和0.99。此外,miRNA相关靶向基因和miRNA-化合物相互作用网络的通路分析表明,这五个miRNA在TGF-β信号通路中发挥作用。

结论

基于模型的PD流出液中miRNA表达可能有助于确定EPS的可能性,并为EPS提供进一步的治疗意见。

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