Cell-free microRNA expression signatures in urine serve as novel noninvasive biomarkers for diagnosis and recurrence prediction of bladder cancer.
Cell-free microRNA expression signatures in urine serve as novel noninvasive biomarkers for diagnosis and recurrence prediction of bladder cancer.
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尿液中的无细胞 microRNA 表达特征可作为膀胱癌诊断和复发预测的新型非侵入性生物标志物
DOI：
10.18632/oncotarget.16586
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发表时间：
2017-06-20
期刊：
影响因子：
--
通讯作者：
Wang C
中科院分区：
文献类型：
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作者：
Du L;Jiang X;Duan W;Wang R;Wang L;Zheng G;Yan K;Wang L;Li J;Zhang X;Pan H;Yang Y;Wang C
尿microRNAs（miRNAs）是膀胱癌（BC）非侵入性诊断的潜在生物标志物。在这项研究中，我们的目的是开发一个尿miRNAs面板诊断和预测复发的BC。对276名BC患者和276名对照的尿液上清液进行了全基因组miRNAs深度测序分析，然后进行了两个阶段的定量实时PCR测定。我们鉴定了一个7-miRNA组（miR-7- 5 p、miR-22- 3 p、miR-29 a-3 p、miR-126- 5 p、miR-200 a-3 p、miR-375和miR-423- 5 p），其提供了BC的高诊断准确性，在训练集和验证集中的AUC分别为0.923和0.916。该组对应的Ta、T1和T2-T4的AUC分别为0.864、0.930和0.978，显著高于尿细胞学的AUC，分别为0.531、0.628和0.724（均p < 0.05）。此外，Kaplan-Meier分析显示，具有高miR-22- 3 p和低miR-200 a-3 p水平的非肌肉浸润性BC（NMIBC）患者的无复发生存率（RFS）更差（分别为p = 0.002和0.040）。多变量考克斯回归分析显示，miR-22- 3 p和miR-200 a-3 p与NMIBC的RFS独立相关（分别为p = 0.024和0.008）。结论：尿miRNAs在膀胱癌的诊断和复发预测中具有重要的临床价值。
Urinary microRNAs (miRNAs) are potential biomarkers for the noninvasive diagnosis of bladder cancer (BC). In this study, we aimed to develop a urinary miRNAs panel for diagnosing and predicting recurrence of BC. Genome-wide miRNAs analysis by deep sequencing followed by two phases of quantitative real-time PCR assays were performed on urine supernatant of 276 BC patients and 276 controls. We identified a seven-miRNA panel (miR-7-5p, miR-22-3p, miR-29a-3p, miR-126-5p, miR-200a-3p, miR-375, and miR-423-5p) that provided high diagnostic accuracy of BC with an AUC of 0.923 and 0.916 in training and validation set, respectively. The corresponding AUCs of this panel for Ta, T1 and T2-T4 were 0.864, 0.930 and 0.978, significantly higher than those of urine cytology, which were 0.531, 0.628 and 0.724, respectively (all p < 0.05). Moreover, Kaplan–Meier analysis showed that nonmuscle-invasive BC (NMIBC) patients with high miR-22-3p and low miR-200a-3p level had worse recurrence-free survival (RFS) (p = 0.002 and 0.040, respectively). Multivariate Cox regression analysis revealed that miR-22-3p and miR-200a-3p were independently associated with RFS of NMIBC (p = 0.024 and 0.008, respectively). In conclusion, our results suggested that urinary miRNAs may have considerable clinical value in diagnosis and recurrence prediction of BC.