Matsuzaki Kyosuke, Fujita Kazutoshi, Tomiyama Eisuke, Hatano Koji, Hayashi Yujiro, Wang Cong, Ishizuya Yu, Yamamoto Yoshiyuki, Hayashi Takuji, Kato Taigo, Jingushi Kentaro, Kawashima Atsunari, Ujike Takeshi, Nagahara Akira, Uemura Motohide, Tsujikawa Kazutake, Nonomura Norio
Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
Department of Urological Immuno-Oncology, Osaka University Graduate School of Medicine, Suita, Japan.
Transl Androl Urol. 2021 Apr;10(4):1918-1927. doi: 10.21037/tau-20-421.
Extracellular vesicles (EVs) including exosomes are present in blood, urine, and saliva and contain proteins, microRNAs, and messenger RNAs. We investigated microRNAs in urinary EVs to discover new biomarkers of prostate cancer (PCa).
We isolated EVs from urine obtained following digital rectal examination (DRE) of 14 men with elevated levels of serum prostate-specific antigen (PSA) [negative biopsy (n=4) and PCa with Gleason scores of 6 (n=3), 7 (n=3), and 8-9 (n=4)]. MicroRNAs extracted from EVs were analyzed by microRNA microarray.
MicroRNAs miR-30b-3p and miR-126-3p were identified as being overexpressed in urinary EVs of the PCa patients versus the biopsy-negative men, but no microRNAs were associated with the Gleason score. In the independent cohort as well, these two microRNAs were overexpressed in urinary EVs from the PCa patients versus the negative-biopsy men. Logistic regression analysis adjusted by age and PSA showed that these two microRNAs were significantly associated with the prediction of PCa in biopsy specimens. Sensitivity and specificity of miR-30b-3p and miR-126-3p for the prediction of PCa were 46.4% and 88.0% and 60.7% and 80.0%, respectively, which were better than those of serum PSA (53.5% and 64.0%, respectively).
MiR-30b-3p and miR-126-3p in urinary EVs could be potential biomarkers of PCa.
包括外泌体在内的细胞外囊泡(EVs)存在于血液、尿液和唾液中,含有蛋白质、微小RNA(miRNAs)和信使RNA。我们研究了尿液EVs中的miRNAs,以发现前列腺癌(PCa)的新生物标志物。
我们从14名血清前列腺特异性抗原(PSA)水平升高的男性患者(阴性活检[n = 4]以及Gleason评分为6[n = 3]、7[n = 3]和8 - 9[n = 4]的PCa患者)经直肠指检(DRE)后获得的尿液中分离出EVs。通过miRNA微阵列分析从EVs中提取的miRNAs。
与活检阴性的男性相比,miR - 30b - 3p和miR - 126 - 3p在PCa患者的尿液EVs中被鉴定为过表达,但没有miRNAs与Gleason评分相关。在独立队列中,与活检阴性的男性相比,这两种miRNAs在PCa患者的尿液EVs中也过表达。经年龄和PSA校正的逻辑回归分析表明,这两种miRNAs与活检标本中PCa的预测显著相关。miR - 30b - 3p和miR - 126 - 3p预测PCa的敏感性和特异性分别为46.4%和88.0%以及60.7%和80.0%,优于血清PSA(分别为53.5%和64.0%)。
尿液EVs中的miR - 30b - 3p和miR - 126 - 3p可能是PCa的潜在生物标志物。