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miRNA 图谱:一种用于准确诊断肾细胞肿瘤的有前途的辅助工具。

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

机构信息

1] Cancer Epigenetics Group, Research Center of the Portuguese Oncology Institute, Rua Doutor António Bernardino Almeida, 4200-072 Porto, Portugal [2] Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.

出版信息

Br J Cancer. 2013 Nov 12;109(10):2646-53. doi: 10.1038/bjc.2013.552. Epub 2013 Oct 15.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

肾细胞肿瘤(RCTs)在临床、形态和遗传上具有异质性。准确识别肾细胞癌(RCCs)并将其与正常组织和良性肿瘤区分开来是必要的。因此,我们旨在确定一组可能有助于 RCTs 诊断的 microRNAs。

方法

收集了 120 例 RCTs(透明细胞 RCC、乳头状 RCC、嗜铬细胞瘤(chRCC)和嗜酸细胞瘤:每个亚型各 30 例)、10 例正常肾组织和 60 例 RCTs 的体外细针抽吸活检(验证组每个亚型各 15 例)的新鲜冷冻组织。通过定量逆转录-PCR 评估 miR-21、miR-141、miR-155、miR-183 和 miR-200b 的表达水平。构建受试者工作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。

结果

与正常组织相比,肾细胞肿瘤显示出 miR-21、miR-141 和 miR-200b 的表达水平显著降低,并且所有 miRs 的表达水平在恶性和良性 RCTs 之间存在显著差异。miR-141 或 miR-200b 的表达分析准确地区分了 RCTs 与正常肾组织、嗜酸细胞瘤与 RCC 和嗜铬细胞瘤与嗜酸细胞瘤。在验证组中证实了诊断性能。有趣的是,miR-21、miR-141 和 miR-155 的表达水平在单因素分析中具有预后意义。

结论

miR-141 或 miR-200b 组合在组织样本中准确地区分 RCC 与正常肾脏和嗜酸细胞瘤,与正常肾脏和嗜酸细胞瘤区分开来,而 miR-21、miR-141 和 miR-155 传递预后信息。这种方法在细针抽吸活检中是可行的,并且可能为常规诊断提供辅助工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f785/3833202/65a004dbabc0/bjc2013552f1.jpg

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