Academic Urology Unit, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
Br J Cancer. 2012 Jun 26;107(1):123-8. doi: 10.1038/bjc.2012.221. Epub 2012 May 29.
Urinary biomarkers are needed to improve the care and reduce the cost of managing bladder cancer. Current biomarkers struggle to identify both high and low-grade cancers due to differing molecular pathways. Changes in microRNA (miR) expression are seen in urothelial carcinogenesis in a phenotype-specific manner. We hypothesised that urinary miRs reflecting low- and high-grade pathways could detect bladder cancers and overcome differences in genetic events seen within the disease.
We investigated urinary samples (n=121) from patients with bladder cancer (n=68) and age-matched controls (n=53). Fifteen miRs were quantified using real-time PCR.
We found that miR is stable within urinary cells despite adverse handling and detected differential expression of 10 miRs from patients with cancer and controls (miRs-15a/15b/24-1/27b/100/135b/203/212/328/1224, ANOVA P<0.05). Individually, miR-1224-3p had the best individual performance with specificity, positive and negative predictive values and concordance of 83%, 83%, 75% and 77%, respectively. The combination of miRs-135b/15b/1224-3p detected bladder cancer with a high sensitivity (94.1%), sufficient specificity (51%) and was correct in 86% of patients (concordance).
The use of this panel in patients with haematuria would have found 94% of urothelial cell carcinoma, while reducing cystoscopy rates by 26%. However, two invasive cancers (3%) would have been missed.
需要尿生物标志物来改善膀胱癌的护理并降低其治疗成本。由于不同的分子途径，当前的生物标志物难以识别高低级别癌症。miRNA（miR）表达的变化以表型特异性的方式出现在尿路上皮癌变中。我们假设反映低级别和高级别途径的尿 miR 可以检测膀胱癌，并克服疾病中所见遗传事件的差异。
我们研究了来自膀胱癌患者（n=68）和年龄匹配的对照者（n=53）的尿液样本（n=121）。使用实时 PCR 定量了 15 种 miR。
我们发现 miR 在尿液细胞中稳定，尽管处理不当，但仍能检测到癌症患者和对照者尿液中 10 种 miR 的差异表达（miR-15a/15b/24-1/27b/100/135b/203/212/328/1224，ANOVA P<0.05）。单独的 miR-1224-3p 具有最佳的个体性能，特异性、阳性和阴性预测值以及一致性分别为 83%、83%、75%和 77%。miR-135b/15b/1224-3p 的组合检测膀胱癌具有高灵敏度（94.1%）、足够的特异性（51%），在 86%的患者中是正确的（一致性）。
在血尿患者中使用该面板可以发现 94%的尿路上皮细胞癌，同时将膀胱镜检查率降低 26%。然而，会错过 2 例侵袭性癌症（3%）。
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