Department of Urology, Zhejiang Cancer Hospital, Hang Zhou, China.
Institute of Cancer Research, Zhejiang Cancer Hospital, Hang Zhou, China.
Eur Urol Focus. 2018 Apr;4(3):412-419. doi: 10.1016/j.euf.2016.09.007. Epub 2016 Oct 14.
Circulating microRNAs (miRNAs) in exosomes are emerging as clinically useful tools for cancer detection. However, little is known about their diagnostic impact in clear-cell renal cell carcinoma (ccRCC).
To investigate whether miRNAs in serum exosomes can serve as biomarkers in ccRCC.
DESIGN, SETTING, AND PARTICIPANTS: Serum samples were obtained from 82 patients with ccRCC and 80 healthy volunteers. Exosomes were extracted and purified to selectively capture exosomes positive for tumor-associated epithelial cell adhesion molecule (EpCAM) via a magnetic bead technique. Total RNA was extracted and expression levels of miR-210, miR-1233, and miR-15a miRNAs were quantified and normalized to U6 levels.
Expression levels were compared using a Mann-Whitney U-test, Friedman test, or Wilcoxon test. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value of exosomal miRNAs for differentiation between ccRCC patients and controls.
Expression levels of exosomal miR-210 and miR-1233 were significantly higher in ccRCC patients than in healthy individuals (both p<0.01). No significant difference was observed for exosomal miR-15a. Exosomal miR-210 and miR-1233 expression levels in different TNM stages were significantly higher than in the controls (all p<0.01). Exosomal miR-210 and miR-1233 expression levels were significantly lower in postoperative than in preoperative samples (both p<0.01). ROC analysis demonstrated that exosomal expression levels distinguished ccRCC patients from healthy individuals with 70% sensitivity and 62.2% specificity for miR-210, and 81% sensitivity and 76% specificity for miR-1233. The retrospective design and lack of other tumor subtypes are limitations of the study.
Serum exosomal miRNAs might represent potential diagnostic biomarkers in ccRCC in the future.
Circulating levels of exosomal microRNAs miR-210 and miR-1233 have potential as biomarkers for diagnostic and monitoring purposes in renal cancer in the future. These molecules can be measured in serum in so-called liquid biopsy.
外泌体中的循环 microRNAs（miRNAs）作为癌症检测的临床有用工具正在出现。然而，关于其在透明细胞肾细胞癌（ccRCC）中的诊断影响知之甚少。
研究血清外泌体中的 miRNAs 是否可作为 ccRCC 的生物标志物。
设计、地点和参与者：采集 82 例 ccRCC 患者和 80 例健康志愿者的血清样本。通过磁珠技术选择性捕获肿瘤相关上皮细胞黏附分子（EpCAM）阳性的外泌体来提取和纯化外泌体。提取总 RNA，定量并归一化为 miR-210、miR-1233 和 miR-15a 等 miRNA 的 U6 水平。
采用 Mann-Whitney U 检验、Friedman 检验或 Wilcoxon 检验比较表达水平。绘制受试者工作特征（ROC）曲线以评估外泌体 miRNA 对区分 ccRCC 患者和对照的诊断价值。
ccRCC 患者血清外泌体 miR-210 和 miR-1233 的表达水平明显高于健康个体（均 p<0.01）。外泌体 miR-15a 则无显著差异。不同 TNM 分期的外泌体 miR-210 和 miR-1233 表达水平明显高于对照组（均 p<0.01）。术后样本的外泌体 miR-210 和 miR-1233 表达水平明显低于术前样本（均 p<0.01）。ROC 分析表明，外泌体表达水平以 70%的灵敏度和 62.2%的特异性区分 ccRCC 患者与健康个体，以 81%的灵敏度和 76%的特异性区分 miR-210 和 miR-1233。该研究的局限性为回顾性设计和缺乏其他肿瘤亚型。
血清外泌体 miRNAs 可能成为未来 ccRCC 的潜在诊断生物标志物。
外泌体 microRNAs（miRNAs）的循环水平具有作为未来肾癌诊断和监测目的的生物标志物的潜力。这些分子可以在所谓的液体活检中通过血清进行测量。
