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用于前列腺癌无创诊断的尿液外泌体微小RNA的鉴定

Identification of Urinary Exosomal miRNAs for the Non-Invasive Diagnosis of Prostate Cancer.

作者信息

Li Zhuo, Li La-Xiu, Diao Yan-Jun, Wang Juan, Ye Yun, Hao Xiao-Ke

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, People's Republic of China.

The National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, Xi'an, Shaanxi 710069, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Jan 6;13:25-35. doi: 10.2147/CMAR.S272140. eCollection 2021.

Abstract

BACKGROUND

Novel and non-invasive biomarkers with higher sensitivity and specificity for the diagnosis of prostate cancer (PCa) is urgently needed. In this study, we used next-generation sequencing (NGS) to characterize the genome-wide exosomal miRNA expression profiling in urine specimens and explored the diagnostic potential of urinary exosomal miRNAs for PCa.

METHODS

Urinary exosomal microRNA expression profiling was performed by next-generation sequencing (NGS) and then validated by quantitative real-time PCR.

RESULTS

Significant downregulation of urinary exosomal miR-375 was observed in PCa patients compared with healthy controls, while the expression levels of urinary exosomal miR-451a, miR-486-3p and miR-486-5p were found to be significantly up-regulated in the PCa patients. Furthermore, the expression level of urinary exosomal miR-375 showed a significant correlation with the clinical T-stage and bone metastasis of patients with PCa (<0.05). Receiver operator characteristic curve demonstrated that the urinary exosomal miR-375, miR-451a, miR-486-3p and miR-486-5p levels can be used to differentiate PCa patients from healthy controls, with area under the curves (AUCs) of 0.788, 0.757, 0.704 and 0.796, respectively. The urinary exosomal miR-375 was found to be superior in discriminating between localized and metastatic PCa with an AUC of 0.806. Moreover, PCa patients can be distinguished from patients with benign prostatic hyperplasia by using a panel combining urinary exosomal miR-375 and miR-451a with an AUC of 0.726.

CONCLUSION

These findings demonstrate that the urinary exosomal miRNAs can serve as novel and non-invasive biomarkers for diagnosing and predicting the progression of PCa.

摘要

背景

迫切需要用于诊断前列腺癌(PCa)的具有更高灵敏度和特异性的新型非侵入性生物标志物。在本研究中,我们使用下一代测序(NGS)来表征尿液标本中全基因组外泌体miRNA表达谱,并探索尿液外泌体miRNA对PCa的诊断潜力。

方法

通过下一代测序(NGS)进行尿液外泌体微小RNA表达谱分析,然后通过定量实时PCR进行验证。

结果

与健康对照相比,PCa患者尿液外泌体miR-375显著下调,而PCa患者尿液外泌体miR-451a、miR-486-3p和miR-486-5p的表达水平显著上调。此外,PCa患者尿液外泌体miR-375的表达水平与患者的临床T分期和骨转移显著相关(<0.05)。受试者操作特征曲线表明,尿液外泌体miR-375、miR-451a、miR-486-3p和miR-486-5p水平可用于区分PCa患者和健康对照,曲线下面积(AUC)分别为0.788、0.757、0.704和0.796。发现尿液外泌体miR-375在区分局限性和转移性PCa方面更具优势,AUC为0.806。此外,通过联合使用尿液外泌体miR-375和miR-451a的组合,AUC为0.726,可将PCa患者与良性前列腺增生患者区分开来。

结论

这些发现表明,尿液外泌体miRNA可作为诊断和预测PCa进展的新型非侵入性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c8f/7797303/c51dc5931e28/CMAR-13-25-g0001.jpg

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