Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma
Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma
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DOI：
10.1007/s00345-010-0633-4
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发表时间：
2011-06-01
影响因子：
3.4
通讯作者：
Junker, Kerstin
中科院分区：
文献类型：
--
作者：
Heinzelmann, Joana;Henning, Brenda;Junker, Kerstin
MicroRNAs （miRNAs）通过调控肿瘤生长、发育、分化和凋亡等多种生物学过程，在肿瘤发生过程中发挥着重要的基因表达调控作用。先前的研究表明，透明细胞肾细胞癌（ccRCC）中特异性mirna的表达发生了改变。但在这种肿瘤类型的发生和转移中的作用几乎是未知的。我们旨在确定与ccRCC患者转移和预后相关的特定miRNA表达模式。我们分离了30例人ccRCC的MiRNA，包括10例非转移性肿瘤、4例3年及以后发生转移的肿瘤和4例原发转移的肿瘤。我们利用微阵列和qRT-PCR分析了miRNA的表达。我们检测到一个区分转移性和非转移性ccRCC的miRNA特征，包括miR-451、miR-221、miR-30a、miR-10b和miR-29a。此外，我们确定了一组12个mirna，如let-7家族，miR-30c, miR-26a，它们在高度侵袭性原发性转移性肿瘤中减少。我们还发现特异性mirna的表达水平与无进展生存期和总生存期之间存在相关性。我们的研究结果表明，特定的mirna参与转移，并对ccRCC的进展产生影响。此外，我们发现了具有早期转移的侵袭性肿瘤的特异性mirna。此外，我们确定了与患者生存相关的候选标志物。因此，使用mirna来预测远处转移的进展和分析原发肿瘤的预后似乎是可能的。
MicroRNAs (miRNAs) play an important role as regulators of gene expression in tumourigenesis by controlling many biological processes in growth, development, differentiation and apoptosis. Previous studies have shown an altered expression of specific miRNAs in clear cell renal cell carcinoma (ccRCC). But the function in cancerogenesis and metastasis in this tumour type is almost unknown. We aimed at identifying specific miRNA expression patterns that are associated with metastasis and prognosis in ccRCC patients.MiRNA of 30 human ccRCC including ten non-metastatic tumours, four tumours with metastasis after 3 years or later and four tumours with primary metastasis was isolated. We analysed the miRNA expression by using microarrays and qRT-PCR.We detected a miRNA signature that distinguishes between metastatic and non-metastatic ccRCC, including miR-451, miR-221, miR-30a, miR-10b and miR-29a. Furthermore, we identified a group of 12 miRNAs, such as let-7 family, miR-30c, miR-26a, which are decreased in highly aggressive primary metastatic tumours. We found also correlations between expression levels of specific miRNAs with progression-free survival and overall survival.Our findings suggest that specific miRNAs are involved in metastasis and have an impact on the progression of the ccRCC. Furthermore, we identified specific miRNAs characterising very aggressive tumours with early metastasis. In addition, we determined candidate markers associated with survival of the patients. Thus, it seems possible to use miRNAs for prediction of progression to distant metastasis and prognosis analysing the primary tumour.