Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Clinical Laboratory, The Dingli Clinical College of Wenzhou Medical University,Wenzhou, China.
Arch Iran Med. 2016 Sep;19(9):645-51.
Abnormal expression of microRNAs (miRNAs) plays an important role in development of several cancer types, including bladder cancer (BCa). However, the relationship between the ratio of miR-181/miR-100 and the prognosis of BCa has not been studied yet. The aim of this study was to evaluate the expression of miR-182, miR-100 and their clinical significance in BCa.
Upregulation of miR-182 and down-regulation of miR-100 were validated in tissue specimens of 134 BCa cases compared with 148 normal bladder epithelia (NBE) specimens using TaqMan-based real-time reverse transcription quantitative PCR (RT-qPCR). The diagnostic and prognostic evaluation of miR-182, miR-100, and miR-182/miR-100 ratio was also performed.
miR-182 was upregulated in BCa and miR-100 was down-regulated in BCa compared with NBE (P < 0.001). The areas under receiver operating characteristic curves (AUCs-ROC) for miR-182 and miR-100 were 0.913 and 0.810, respectively. However, miR-182/miR-100 ratio increased the diagnostic performance, yielding an AUC of 0.981 (97.01% sensitivity and 90.54% specificity). Moreover, miR-182/miR-100 ratio was associated with pT-stage, histological grade, BCa recurrence and carcinoma in situ (P < 0.05 for all). Multivariate Cox regression analysis indicated that miR-182/miR-100 ratio was an independent prognostic factor for overall survival (Hazard ratio: 7.142; 95% CI: 2.106 - 9.891; P < 0.01). Furthermore, Kaplan-Meier curve analysis revealed that high-level of miR-182/miR-100 ratio was significantly correlated with shortened survival time for BCa patients (P < 0.01).
The miR-182/miR-100 ratio may serve as a novel promising biomarker for diagnosis and survival prediction in BCa. Further studies are needed to elucidate the role of miR-182/miR-100 ratio as a non‑invasive diagnostic tool for BCa.
微小 RNA（miRNA）的异常表达在多种癌症类型的发生发展中发挥着重要作用，包括膀胱癌（BCa）。然而，miR-181/miR-100 的比值与 BCa 预后之间的关系尚未被研究。本研究旨在评估 miR-182、miR-100 在 BCa 中的表达及其临床意义。
采用 TaqMan 实时定量 RT-PCR（RT-qPCR）方法，在 134 例 BCa 组织标本和 148 例正常膀胱上皮（NBE）标本中验证 miR-182 的上调和 miR-100 的下调。还对 miR-182、miR-100 和 miR-182/miR-100 比值的诊断和预后评估进行了分析。
miR-182 在 BCa 中上调，miR-100 在 BCa 中下调，与 NBE 相比（P < 0.001）。miR-182 和 miR-100 的受试者工作特征曲线下面积（AUC-ROC）分别为 0.913 和 0.810。然而，miR-182/miR-100 比值提高了诊断效能，AUC 为 0.981（97.01% 的敏感性和 90.54% 的特异性）。此外，miR-182/miR-100 比值与 pT 分期、组织学分级、BCa 复发和原位癌有关（所有 P < 0.05）。多因素 Cox 回归分析表明，miR-182/miR-100 比值是总生存的独立预后因素（危险比：7.142；95%CI：2.106-9.891；P < 0.01）。此外，Kaplan-Meier 曲线分析显示，高水平的 miR-182/miR-100 比值与 BCa 患者的生存时间缩短显著相关（P < 0.01）。
miR-182/miR-100 比值可能成为 BCa 诊断和生存预测的一种新的有前途的生物标志物。需要进一步的研究来阐明 miR-182/miR-100 比值作为 BCa 无创诊断工具的作用。
