Department of Urology, Chungbuk National University College of Medicine, Cheongju, Republic of Korea.
Int J Oncol. 2012 Nov;41(5):1871-8. doi: 10.3892/ijo.2012.1622. Epub 2012 Sep 6.
miRNAs are small, non-coding RNAs that play important roles in various biological processes. The aims of our study were to investigate whether cell-free miRNAs can be measured in urine samples and might be an accurate biomarker of bladder cancer. Datasets of GSE20418 and GSE19717 were used for analysis, and two miRNAs, miR-145 and miR-200a, were selected for study. A total of 207 patients with primary transitional cell carcinoma of the urinary bladder and 144 healthy normal controls were enrolled. Using quantitative PCR, the levels of miR-145 and miR-200a in urine were measured and compared with the clinicopathological features of bladder cancer. According to our experiments, cell-free miRNAs were present in urine and were stable. Assessment of miR-145 levels was able to distinguish bladder cancer patients from non-cancer controls (77.8% sensitivity and 61.1% specificity for NMIBC, AUC 0.729; 84.1 and 61.1% for MIBC, respectively, AUC 0.790) and showed good correlation with grade (p=0.048). In addition, miR-200a was shown to be an independent predictor of NMIBC recurrence by multivariate analysis (OR 0.449, 95% CI 0.239‑0.842, p=0.013). A higher risk of recurrence was observed among patients with a lower miR-200a level compared to patients with higher miR-200a levels (log-rank test, p=0.040). Urinary cell-free miRNAs show promise as noninvasive biomarkers for diagnosis and recurrence of bladder cancer.
miRNAs 是一类小的非编码 RNA,在各种生物过程中发挥重要作用。本研究旨在探讨细胞外游离 miRNA 是否可在尿液样本中测量,是否可作为膀胱癌的准确生物标志物。使用 GSE20418 和 GSE19717 数据集进行分析,选择了两个 miRNA(miR-145 和 miR-200a)进行研究。共纳入 207 例原发性移行细胞膀胱癌患者和 144 例健康正常对照者。采用定量 PCR 检测尿液中 miR-145 和 miR-200a 的水平,并与膀胱癌的临床病理特征进行比较。根据我们的实验,细胞外游离 miRNA 存在于尿液中且稳定。miR-145 水平的评估能够区分膀胱癌患者与非癌症对照者(非肌层浸润性膀胱癌的敏感性为 77.8%,特异性为 61.1%,AUC 为 0.729;肌层浸润性膀胱癌的敏感性为 84.1%,特异性为 61.1%,AUC 为 0.790),且与分级呈良好相关性(p=0.048)。此外,miR-200a 通过多变量分析被证明是非肌层浸润性膀胱癌复发的独立预测因子(OR 0.449,95%CI 0.239-0.842,p=0.013)。与 miR-200a 水平较高的患者相比,miR-200a 水平较低的患者复发风险更高(对数秩检验,p=0.040)。游离于细胞外的尿液 miRNA 有望成为膀胱癌诊断和复发的非侵入性生物标志物。