Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Department of Urologic Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Urol Oncol. 2019 Mar;37(3):184.e1-184.e7. doi: 10.1016/j.urolonc.2018.10.014. Epub 2018 Nov 13.
Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease characterized by a high primary tumor recurrence rate. Current prognostic systems used for predicting recurrence in individual patients have limitations and do not consider the biological background of this tumor type. Our study aimed to find microRNAs (miRNAs) associated with NMIBC recurrence.
Seventy-eight NMIBC patients were prospectively enrolled and divided into exploratory and validation cohorts. Out of these patients, 32 developed recurrence within 18 months after surgery, while 46 did not show any sign of recurrence after 30 months. Expression profiles of 2,578 miRNAs were obtained using Affymetrix miRNA microarrays and candidate miRNAs validated using the individual quantitative reverse-transcription polymerase chain reaction (qRT-PCR).
The expression profiling revealed a set of 137 miRNAs differentially expressed between NMIBC patients with and without recurrence (P < 0.05). In the validation phase, miR-34a-3p had a significantly higher expression in tumors of NMIBC patients without recurrence (P = 0.0155). Decreased expression of miR-34a-3p was associated with significantly shorter recurrence-free survival (P = 0.009). Cox regression analysis confirmed that miR-34a-3p is an independent biomarker associated with a lower risk of recurrence (hazard ratio (HR) = 0.3184, 95% confidence interval = 0.003-0.681, P = 0.0258). Combination of miR-34a-3p and European Organization for Research and Treatment of Cancer risk score into one predictive model enabled to predict individual risk of recurrence with high statistical significance and analytical performance (P < 0.0001; area under curve = 0.8368; sensitivity 83%, and specificity 75%).
Our data suggest that miR-34a-3p is an independent biomarker of NMIBC recurrence and a promising candidate for further independent validations as an additional factor to improve predictive value of European Organization for Research and Treatment of Cancer nomogram.
非肌肉浸润性膀胱癌（NMIBC）是一种异质性疾病，其特征为原发性肿瘤复发率高。目前用于预测个体患者复发的预后系统存在局限性，并且未考虑到这种肿瘤类型的生物学背景。本研究旨在寻找与 NMIBC 复发相关的 microRNAs（miRNAs）。
前瞻性纳入 78 例 NMIBC 患者，并将其分为探索性和验证性队列。这些患者中有 32 例在手术后 18 个月内复发，而 46 例在 30 个月后无任何复发迹象。使用 Affymetrix miRNA 微阵列获得 2578 个 miRNA 的表达谱，并使用个体定量逆转录聚合酶链反应（qRT-PCR）验证候选 miRNA。
表达谱分析显示，在有或无复发的 NMIBC 患者之间存在一组 137 个 miRNA 表达差异（P < 0.05）。在验证阶段，miR-34a-3p 在无复发 NMIBC 患者的肿瘤中表达显著升高（P = 0.0155）。miR-34a-3p 表达降低与无复发生存时间显著缩短相关（P = 0.009）。Cox 回归分析证实，miR-34a-3p 是与复发风险降低相关的独立生物标志物（危险比（HR）= 0.3184，95%置信区间= 0.003-0.681，P = 0.0258）。miR-34a-3p 和欧洲癌症研究与治疗组织（EORTC）风险评分的组合纳入一个预测模型，可实现对个体复发风险的高统计学意义和分析性能的预测（P < 0.0001；曲线下面积（AUC）= 0.8368；敏感性 83%，特异性 75%）。
我们的数据表明，miR-34a-3p 是非肌肉浸润性膀胱癌复发的独立生物标志物，是作为欧洲癌症研究与治疗组织列线图的附加因素来提高预测价值的有前途的候选物，值得进一步独立验证。
