Reduced expression of Dicer associated with poor prognosis in lung cancer patients
Reduced expression of Dicer associated with poor prognosis in lung cancer patients
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DOI：
10.1111/j.1349-7006.2005.00015.x
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发表时间：
2005-02-01
期刊：
影响因子：
5.7
通讯作者：
Takahashi, T
中科院分区：
文献类型：
--
作者：
Karube, Y;Tanaka, H;Takahashi, T
新的证据表明，microRNA是一种保守、丰富且小的调节RNA，可能参与人类癌症的发病机制。我们最近报道，let-7 的表达在肺癌中经常降低，并且 let-7 表达的降低与较短的患者生存期显着相关。双链 RNA 特异性核酸内切酶家族的两个成员 Dicer 和 Drosha 通过逐步过程将 microRNA 的前体形式转化为其成熟形式。在本研究中，我们检测了 67 个非小细胞肺癌病例中这些基因的表达水平，并首次发现部分肺癌中 Dicer 表达水平降低，对手术治疗病例的生存具有显着的预后影响。值得注意的是，多变量COX回归分析表明，Dicer的预后影响（P = 0.001）似乎与疾病分期无关（P = 0.001），而逻辑回归分析表明，即使在校正其他参数后，低分化肿瘤中Dicer表达减少的较高发生率仍然显着（P = 0.02）。鉴于 Dicer 在各种细胞过程中的基本和多种生物学作用，我们的结果表明 Dicer 表达减少参与了肺癌的发展，因此需要进一步研究其潜在机制，这有望增强对这种致命癌症的分子发病机制的理解。
Emerging evidence suggests that microRNA, which are well-conserved, abundant and small regulatory RNA, may be involved in the pathogenesis of human cancers. We recently reported that expression of let-7 was frequently reduced in lung cancers, and that reduced let-7 expression was significantly associated with shorter patient survival. Two members of the double-stranded RNA-specific endonuclease family, Dicer and Drosha, convert precursor forms of microRNA into their mature forms using a stepwise process. In the present study, we examined expression levels of these genes in 67 non-small cell lung cancer cases, and found for the first time that Dicer expression levels were reduced in a fraction of lung cancers with a significant prognostic impact on the survival of surgically treated cases. It should be noted that multivariate COX regression analysis showed that the prognostic impact of Dicer (P = 0.001) appears to be independent of disease stage (P = 0.001), while logistic regression analysis demonstrated that the higher incidence of reduced Dicer expression in poorly differentiated tumors remained significant even after correction for other parameters (P = 0.02). Given the fundamental and multiple biological roles of Dicer in various cellular processes, our results suggest the involvement of reduced Dicer expression in the development of lung cancers, thus warranting further investigations of the underlying mechanisms, which can be expected to enhance understanding of the molecular pathogenesis of this fatal cancer.