The Clinical Utility of miR-21 as a Diagnostic and Prognostic Marker for Renal Cell Carcinoma

The Clinical Utility of miR-21 as a Diagnostic and Prognostic Marker for Renal Cell Carcinoma
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DOI:
10.1016/j.jmoldx.2012.02.003
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发表时间:
2012-07-01
影响因子:
4.1
通讯作者:
Yousef, George M.
Yousef, George M.
中科院分区:
医学3区
文献类型:
--
作者:
Faragalla, Hala;Youssef, Youssef M.;Yousef, George M.

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肾细胞癌(RCC)是最常见的肾脏肿瘤。越来越多的证据表明,microRNAs在肾癌中表达异常,是肾癌发病的重要因素。MIR-21是一种已知的癌基因,在许多类型的癌症中具有促癌作用。在本研究中,我们分析了121例正常肾脏和不同类型肾细胞癌的miR-21,包括透明细胞(CcRCC)、乳头状细胞癌(PRCC)、嫌色细胞(ChRCC)和嗜酸细胞瘤。提取总RNA,用miR-21特异性探针进行实时定量RT-PCR检测miR-21的表达。与正常肾组织相比,肾癌组织中miR-21的表达显著上调。肾细胞癌各亚型间的表达水平有显著差异,其中ccRCC和pRCC亚型的表达水平最高。MIR-21表达与慢性肾细胞癌和嗜酸细胞瘤鉴别诊断的特异性为90%(95%CI,63.9%~98.1%),敏感性为83%(95%CI,53.5%~97.6%)。MiR-21水平显著升高与肿瘤的分期和分级有关。MiR-21阳性的患者无病存活率和总存活率在统计学上显着缩短。因此,miR-21在肾癌中表达上调,其表达水平可作为鉴别ccRCC和pRCC与chRCC和嗜酸细胞瘤的诊断指标。此外,尽管它不独立于肿瘤的分期和分级,但仍有可能成为肾癌的预后标志物。(摩尔诊断杂志,2012年,14:385-302;http://dx.doi.org/10.1016/j.jmoldx.2012.02.003)
Renal cell carcinoma (RCC) is the most common neoplasm of the kidney. Increasing evidence suggests that microRNAs are dysregulated in RCC and are important factors in RCC pathogenesis. miR-21 is a known oncogene with tumor-promoting effects in many types of cancer. In this study, we analyzed miR-21 in 121 cases of healthy kidney and different RCC subtypes, including clear cell (ccRCC), papillary (pRCC), chromophobe (chRCC), and oncocytoma. Total RNA was extracted, and the expression of miR-21 was measured with real-time quantitative RT-PCR using miR-21 specific probes. The expression of miR-21 was significantly up-regulated in RCC compared with healthy kidney. There was a significant difference in the expression levels between RCC subtypes, with the highest levels of expression in ccRCC and pRCC subtypes. miR-21 expression distinguished ccRCC and pRCC from chRCC and oncocytoma with 90% specificity (95% CI, 63.9% to 98.1%) and 83% sensitivity (95% CI, 53.5% to 97.6%). Significantly higher miR-21 levels were associated with higher stage and grade. Patients who were miR-21 positive had statistically significant shorter disease-free and overall survival rates. Thus, miR-21 is up-regulated in RCC, and its expression levels can be used as a diagnostic marker to distinguish ccRCC and pRCC from chRCC and oncocytoma. Moreover, it has potential as a prognostic marker in RCC, although it is not independent of tumor stage and grade. (J Mol Diagn 2012, 14:385-302; http://dx.doi.org/10.1016/j.jmoldx.2012.02.003)