Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-based Approach.
Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-based Approach.
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DOI：
10.3390/cancers12113133
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发表时间：
2020-10-26
期刊：
影响因子：
5.2
通讯作者：
Ciminale V
中科院分区：
文献类型：
--
作者：
Cavallari I;Grassi A;Del Bianco P;Aceti A;Zaborra C;Sharova E;Bertazzolo I;D'Agostino DM;Iafrate M;Ciminale V
大多数膀胱癌患者在恶性细胞侵入膀胱肌壁之前被诊断出来，可以通过手术治疗。然而，这些患者的疾病复发和进展为肌肉浸润性疾病的风险很高，并且必须定期接受膀胱镜检查和尿细胞学检查，这些程序对患者和医疗保健系统来说都是繁重的。我们着手确定一种后续/风险评估测试，该测试分析尿液样本中特定类别的RNA分子（microRNA）的水平。结果导致在尿液样本中发现了一组microRNA，可以高准确性地识别高危膀胱癌患者并预测无事件生存期。因此，这种尿液microRNA检测有望成为目前膀胱癌随访方法的非侵入性替代方法。 对膀胱癌（BCa）患者预后分层的稳健非侵入性检测需求很高。在对BCa研究进行全面分析后，我们选择了一组29种microRNA（miRNAs），并使用RT-qPCR分析了63例BCa患者（32例复发高危病例和31例低风险病例）和37例健康对照的前瞻性队列中尿液和血浆样本中的miRNAs水平。为了设计适合于大规模测试的测定，我们应用分级管道来选择不受混杂因素如血尿和尿比重影响并且超过严格截止标准（倍数变化> 2.5并且p值< 0.005）的miRNA。使用基于miR-34 a-5 p、miR-200 a-3 p和miR-193 a-5 p的尿液水平的两步决策树，针对miR-125 b-5 p标准化，患者可以被分类为高风险或低风险，灵敏度为0.844，特异性为0.806，准确度为0.825。此外，单变量考克斯比例风险回归分析表明，miR-29 a-3 p、miR-34 a-5 p、miR-193 a-5 p、miR-200 c-3 p、miR-205- 5 p和miR-532- 5 p的尿液水平升高与无事件生存期缩短相关（风险比> 3.1，p值< 0.05）。总而言之，我们的研究结果表明，测量这些miRNA的尿液水平可以为BCa患者的风险评估提供一种新型的具有成本效益的非侵入性测试。
The majority of patients with bladder cancer are diagnosed before the malignant cells invade the bladder’s muscle wall, and can be treated with surgery. These patients are nevertheless at high risk of disease recurrence and progression to muscle-invasive disease, and must undergo periodic cystoscopy and urine cytology, procedures that are burdensome for the patient and for the healthcare system. We set out to identify a follow-up/risk assessment test that analyzes the levels of a specific class of RNA molecules (microRNAs) in urine samples. Results led to the discovery of a panel of microRNAs in urine samples that identifies high-risk bladder cancer patients with high accuracy and predicts event-free survival. This urine microRNA assay thus holds promise as a noninvasive alternative to current methods for bladder cancer follow-up. Robust non-invasive tests for prognostic stratification of bladder cancer (BCa) patients are in high demand. Following a comprehensive analysis of studies on BCa, we selected a panel of 29 microRNAs (miRNAs) and analyzed their levels in urine and plasma samples in a prospective cohort of 63 BCa patients (32 at high risk of recurrence and 31 low-risk cases) and 37 healthy controls using RT-qPCR. To design an assay suitable for large-scale testing, we applied a hierarchical pipeline to select the miRNAs that were not affected by confounding factors such as haematuria and urine specific gravity, and exceeded stringent cut-off criteria (fold change > 2.5 and p-value < 0.005). Using a two-step decision tree based on the urine levels of miR-34a-5p, miR-200a-3p and miR-193a-5p, normalized against miR-125b-5p, patients could be classified as high- or low-risk with a sensitivity of 0.844, specificity of 0.806 and accuracy of 0.825. Furthermore, univariate Cox proportional hazards regression analyses indicated that increased urine levels of miR-29a-3p, miR-34a-5p, miR-193a-5p, miR-200c-3p, miR-205-5p and miR-532-5p were associated with a shorter event-free survival (hazard ratios > 3.1, p-value < 0.05). Taken together, our findings suggest that measuring the urine levels of these miRNAs could provide a novel cost-effective, noninvasive test for risk assessment of BCa patients.
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5.6
作者：
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