MicroRNA Expression Profiles in Upper Tract Urothelial Carcinoma Differentiate Tumor Grade, Stage, and Survival: Implications for Clinical Decision-Making
MicroRNA Expression Profiles in Upper Tract Urothelial Carcinoma Differentiate Tumor Grade, Stage, and Survival: Implications for Clinical Decision-Making
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DOI：
10.1016/j.urology.2018.10.004
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发表时间：
2019-01-01
期刊：
影响因子：
2.1
通讯作者：
Reiger-Christ, Kimberly M.
中科院分区：
文献类型：
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作者：
Browne, Brendan M.;Stensland, Kristian D.;Reiger-Christ, Kimberly M.
目的探讨微RNA（microRNA，miRNA）在上尿路上皮癌（upper tract uroithelial carcinoma，UTUC）诊断中的价值。方法从2个机构的157例根治性肾输尿管切除术标本中分离miRNA。检测了高级别与低级别肿瘤以及肌肉浸润性与非肌肉浸润性肿瘤的miRNA相对表达。结果用于鉴定高级别UTUC的优化模型包括miR-29 b-2- 5 p、miR-18 a-5 p、miR-223- 3 p和miR-199 a-5 p，产生的灵敏度为83%，特异性为85%，并产生曲线下面积为0.86的受试者工作特征（ROC）曲线。类似地，用于预测>= pT 2疾病的模型分类器并入miR-10 b-5 p、miR-26 a-5 p-5 p、miR-31- 5 p和miR-146 b-5 p，产生64%的灵敏度、96%的特异性和0.90的曲线下面积。miR-10a-5 p、miR-30 c-5 p和miR-10 b-5 p的组合最能反映RFS，而miR-10a-5 p、miR-199 a-5 p、miR-30 c-5 p和miR-10 b-5 p的组合最能预测OS。此外，UTUC miRNA的差异表达产生了用于预测RFS和OS的稳健分类器，这可能有助于识别最受益于辅助治疗的患者。(C)2018爱思唯尔公司
OBJECTIVE To evaluate microRNA (miRNA) biomarkers tor upper tract urothelial carcinoma (UTUC.) to improve risk stratification.METHODS miRNA was isolated from 157 radical nephroureterectomy specimens from 2 institutions. The relative expression of miRNA was examined for high grade vs low grade tumors as well as muscle invasive vs nonmuscle invasive tumors. Recurrence free survival (RFS) and overall survival (OS) were also stratified using relative expression of specific miRNA.RESULTS The optimized model to identify high grade UTUC included miR-29b-2-5p, miR-18a-5p, miR-223-3p, and miR-199a-5p, generating a sensitivity of 83%, specificity of 85%, and generated a receiver operating characteristic (ROC) curve with area-under-the-curve of 0.86. Similarly, the model classifier for predicting >= pT2 disease incorporated miR-10b-5p, miR-26a-5p-5p, miR-31-5p, and miR-146b-5p, producing a sensitivity of 64%, specificity of 96%, and area-under-the-curve of 0.90. RFS was best reflected by a combination of miR-10a-5p, miR-30c-5p, and miR-10b-5p, while OS was best predicted by miR-10a-5p, miR-199a-5p, miR-30c-5p, and miR-10b-5p.CONCLUSION High-grade vs low-grade as well as muscle invasive vs nonmuscle invasive UTUC can be reliable distinguished with unique miRNA signatures. Furthermore, differential expression of UTUC miRNA produces robust classifiers for predicting RFS and OS that may help identify patients who would most benefit from adjuvant therapies. (C) 2018 Elsevier Inc.