MicroRNA profile: a promising ancillary tool for accurate renal cell tumour diagnosis.

MicroRNA profile: a promising ancillary tool for accurate renal cell tumour diagnosis.
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DOI:
10.1038/bjc.2013.552
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发表时间:
2013-11-12
影响因子:
8.8
通讯作者:
Jeronimo, C.
Jeronimo, C.
中科院分区:
医学1区
文献类型:
--
作者:
Silva-Santos, R. M.;Costa-Pinheiro, P.;Luis, A.;Antunes, L.;Lobo, F.;Oliveira, J.;Henrique, R.;Jeronimo, C.

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肾细胞肿瘤(RCT)在临床、形态和遗传上具有异质性。准确识别肾细胞癌(RCC)及其与正常组织和良性肿瘤的区别是强制性的。因此,我们的目标是定义一组可能有助于RCT诊断的microRNAs。收集120例肾癌(透明细胞肾癌、乳头状肾癌、嫌色肾癌和嗜酸细胞瘤各30例)新鲜冰冻组织、10例正常肾组织和60例体外细针抽吸活组织标本(每个亚型验证集15例)。用定量逆转录-聚合酶链式反应检测miR-21、miR-141、miR-155、miR-183和miR-200b的表达水平。构建受试者操作员特征曲线,并计算曲线下面积以评估诊断性能。计算疾病特异性生存曲线和包含所有显著变量的COX回归模型。肾细胞肿瘤组织中miR-21、miR-141和miR-200b的表达水平明显低于正常组织,且恶性和良性RCT之间miR-21、miR-141和miR-200b的表达水平存在显著差异。MiR-141或miR-200b的表达分析能准确区分RCT与正常肾组织、嗜酸细胞瘤与肾癌、肾细胞癌与嗜酸细胞瘤。在验证集中确认了诊断性能。有趣的是,在单因素分析中,miR-21、miR-141和miR-155的表达水平对预后有意义。MiR-141或miR-200b能在组织标本中准确区分肾细胞癌与正常肾和嗜酸细胞瘤,区分正常肾和嗜酸细胞瘤,而miR-21、miR-141和miR-155则传达预后信息。这种方法在细针抽吸活组织检查中是可行的,并可能为常规诊断提供辅助工具。
Renal cell tumours (RCTs) are clinically, morphologically and genetically heterogeneous. Accurate identification of renal cell carcinomas (RCCs) and its discrimination from normal tissue and benign tumours is mandatory. We, thus, aimed to define a panel of microRNAs that might aid in the diagnostic workup of RCTs. Fresh-frozen tissues from 120 RCTs (clear-cell RCC, papillary RCC, chromophobe RCC (chRCC) and oncocytomas: 30 cases each), 10 normal renal tissues and 60 cases of ex-vivo fine-needle aspiration biopsies from RCTs (15 of each subtype validation set) were collected. Expression levels of miR-21, miR-141, miR-155, miR-183 and miR-200b were assessed by quantitative reverse transcription–PCR. Receiver operator characteristic curves were constructed and the areas under the curve were calculated to assess diagnostic performance. Disease-specific survival curves and a Cox regression model comprising all significant variables were computed. Renal cell tumours displayed significantly lower expression levels of miR-21, miR-141 and miR-200b compared with that of normal tissues, and expression levels of all miRs differed significantly between malignant and benign RCTs. Expression analysis of miR-141 or miR-200b accurately distinguished RCTs from normal renal tissues, oncocytoma from RCC and chRCC from oncocytoma. The diagnostic performance was confirmed in the validation set. Interestingly, miR-21, miR-141 and miR-155 expression levels showed prognostic significance in a univariate analysis. The miR-141 or miR-200b panel accurately distinguishes RCC from normal kidney and oncocytoma in tissue samples, discriminating from normal kidney and oncocytoma, whereas miR-21, miR-141 and miR-155 convey prognostic information. This approach is feasible in fine-needle aspiration biopsies and might provide an ancillary tool for routine diagnosis.
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