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尿外泌体 microRNA 谱分析在中危前列腺癌中的应用。

Urinary exosomal microRNA profiling in intermediate-risk prostate cancer.

机构信息

Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Republic of Korea.

出版信息

Sci Rep. 2021 Apr 1;11(1):7355. doi: 10.1038/s41598-021-86785-z.

Abstract

MicroRNAs (miRNAs) of urine exosomes have emerged as biomarkers for urological cancers, owing to their high stability. MiRNAs have been linked to factors associated with aggressive prostate cancer such as biochemical recurrence (BCR) and metastasis. In this study, we aimed to identify urinary exosomal miRNAs as prognostic markers associated with BCR in intermediate-risk prostate cancer. We profiled the expression levels of miRNAs via next generation sequencing in urinary exosomes from 21 non-BCR patients and 6 BCR patients of intermediate-risk prostate cancer. A total of 21 urinary exosomal miRNAs were found to be differentially expressed (> twofold) in BCR patients compared to non-BCR patients. For external validation, we validated these results using quantitative reverse transcription PCR in an independent cohort of 28 non-BCR patients and 26 BCR patients. A validation analysis revealed that three miRNAs (miR-26a-5p, miR-532-5p, and miR-99b-3p) were upregulated in exosomes from BCR patients. The univariate and multivariate Cox regression analyses showed that miR-532-5p was an important predictive factor for BCR of intermediate-risk prostate cancer. In conclusion, miR-532-5p in urine exosomes might be a potential biomarker for predicting BCR, which is a poor prognosis in patients with intermediate-risk prostate cancer. Further research is needed on the biological functions and mechanisms of this miRNA.

摘要

尿液外泌体中的 microRNAs(miRNAs)因其高稳定性而成为泌尿系统癌症的生物标志物。miRNAs 与前列腺癌的侵袭性相关因素有关,如生化复发(BCR)和转移。在这项研究中,我们旨在确定与中间风险前列腺癌 BCR 相关的尿液外泌体 miRNAs 作为预后标志物。我们通过下一代测序对 21 名非 BCR 患者和 6 名中间风险前列腺癌 BCR 患者的尿液外泌体中的 miRNA 表达水平进行了分析。与非 BCR 患者相比,BCR 患者的 21 种尿液外泌体 miRNA 的表达水平差异显著(>两倍)。为了进行外部验证,我们使用定量逆转录 PCR 在一个独立的 28 名非 BCR 患者和 26 名 BCR 患者的队列中验证了这些结果。验证分析表明,miR-26a-5p、miR-532-5p 和 miR-99b-3p 三种 miRNA 在 BCR 患者的外泌体中上调。单因素和多因素 Cox 回归分析表明,miR-532-5p 是中间风险前列腺癌 BCR 的重要预测因子。总之,尿液外泌体中的 miR-532-5p 可能是预测中间风险前列腺癌 BCR 的潜在生物标志物,BCR 是该类患者预后不良的标志。需要进一步研究该 miRNA 的生物学功能和机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/384b/8016942/480b7f44bdc5/41598_2021_86785_Fig1_HTML.jpg

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