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外泌体和非外泌体来源的尿液微小RNA在前列腺癌检测和预后中的作用

Exosomal and Non-Exosomal Urinary miRNAs in Prostate Cancer Detection and Prognosis.

作者信息

Foj Laura, Ferrer Ferran, Serra Marta, Arévalo Antonio, Gavagnach Montserrat, Giménez Nuria, Filella Xavier

机构信息

Department of Biochemistry and Molecular Genetics (CDB), Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain.

Department of Radiotherapy, Institut Català d'Oncologia, IDIBELL, Department of Clinical Sciences-Bellvitge Health Sciences Campus, University of Barcelona, L'Hospitalet de Llobregat, Catalonia, Spain.

出版信息

Prostate. 2017 May;77(6):573-583. doi: 10.1002/pros.23295. Epub 2016 Dec 19.

DOI:10.1002/pros.23295
PMID:27990656
Abstract

BACKGROUND

MicroRNAs (miRNAs) are non-coding small RNAs, involved in post-transcriptional regulation of many target genes.

METHODS

Five miRNAs that have been consistently found deregulated in PCa (miR-21, miR-141, miR-214, miR-375, and let-7c) were analyzed in urinary pellets from 60 prostate cancer (PCa) patients and 10 healthy subjects by qRT-PCR. Besides, urinary exosomes were isolated by differential centrifugation and analyzed for those miRNAs.

RESULTS

Significant upregulation of miR-21, miR-141, and miR-375 was found comparing PCa patients with healthy subjects in urinary pellets, while miR-214 was found significantly downregulated. Regarding urinary exosomes, miR-21 and miR-375 were also significantly upregulated in PCa but no differences were found for miR-141. Significant differences were found for let-7c in PCa in urinary exosomes while no differences were observed in urinary pellets. A panel combining miR-21 and miR-375 is suggested as the best combination to distinguish PCa patients and healthy subjects, with an AUC of 0.872. Furthermore, the association of miRNAs with clinicopathological characteristics was investigated. MiR-141 resulted significantly correlated with Gleason score in urinary pellets and let-7c with clinical stage in urinary exosomes. Additionally, miR-21, miR-141, and miR-214 were found significantly deregulated in intermediate/high-risk PCa versus low-risk/healthy subjects in urinary pellets. Significant differences between both groups were found in urinary exosomes for miR-21, miR-375, and let-7c.

CONCLUSIONS

These findings suggest that the analysis of miRNAs-especially miRNA-21 and miR-375- in urine could be useful as biomarkers in PCa. Prostate 77: 573-583, 2017. © 2016 Wiley Periodicals, Inc.

摘要

背景

微小RNA(miRNA)是非编码小RNA,参与许多靶基因的转录后调控。

方法

通过qRT-PCR分析了60例前列腺癌(PCa)患者和10名健康受试者尿沉渣中5种在PCa中一直被发现失调的miRNA(miR-21、miR-141、miR-214、miR-375和let-7c)。此外,通过差速离心法分离尿外泌体,并对这些miRNA进行分析。

结果

与健康受试者相比,PCa患者尿沉渣中miR-21、miR-141和miR-375显著上调,而miR-214显著下调。关于尿外泌体,PCa中miR-21和miR-375也显著上调,但miR-141未发现差异。PCa患者尿外泌体中let-7c存在显著差异,而尿沉渣中未观察到差异。建议将miR-21和miR-375组合作为区分PCa患者和健康受试者的最佳组合,曲线下面积(AUC)为0.872。此外,还研究了miRNA与临床病理特征的相关性。miR-141在尿沉渣中与Gleason评分显著相关,let-7c在尿外泌体中与临床分期相关。此外,在尿沉渣中,与低风险/健康受试者相比,miR-21、miR-141和miR-214在中/高风险PCa中显著失调。两组在尿外泌体中miR-21、miR-375和let-7c存在显著差异。

结论

这些发现表明,尿液中miRNA尤其是miR-21和miR-375的分析可能作为PCa的生物标志物。《前列腺》77: 573 - 583, 2017。© 2016威利期刊公司。

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