Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype.
Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype.
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DOI：
10.1038/sj.bjc.6605193
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发表时间：
2009-08-18
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
DICER是一种核糖核酸酶，是微小RNA和小干扰RNA生物发生所需的关键酶，对哺乳动物的发育和细胞分化都是必不可少的。最近的证据表明，迪格尔也可能参与了肿瘤的发生。然而，还没有研究在乳腺癌的RNA和蛋白质水平上检测DICER的临床意义。在这项研究中，利用组织微阵列和定量逆转录-聚合酶链式反应，在乳腺癌细胞系、乳腺癌进展细胞模型以及从长期随访的患者中获得的两组具有良好特征的乳腺癌样本中，评估了DICER表达的生物学和预后价值。我们发现乳腺肿瘤中DICER蛋白的表达与激素受体状态和肿瘤亚型显著相关(ER P=0.008；PR P=0.019；癌亚型P=0.023，腔A P=0.0174)。在转移性疾病中，DICER mRNA的表达似乎是一个独立的预后影响因素(危险性比=3.36，P=0.0032)。在乳腺癌细胞系中，在具有间充质表型的细胞和乳腺癌细胞系的转移性骨衍生物中发现较低的DICER表达。这些发现表明，DICER表达下调可能与肿瘤的转移性扩散有关。评估DICER的表达可能有助于预测乳腺癌患者的远处转移。
Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation. Recent evidence indicates that Dicer may also be involved in tumourigenesis. However, no studies have examined the clinical significance of Dicer at both the RNA and the protein levels in breast cancer. In this study, the biological and prognostic value of Dicer expression was assessed in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterised sets of breast carcinoma samples obtained from patients with long-term follow-up using tissue microarrays and quantitative reverse transcription–PCR. We have found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumours (ER P=0.008; PR P=0.019; cancer subtype P=0.023, luminal A P=0.0174). Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio=3.36, P=0.0032). In the breast cancer cell lines, lower Dicer expression was found in cells harbouring a mesenchymal phenotype and in metastatic bone derivatives of a breast cancer cell line. These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours. Assessment of Dicer expression may facilitate prediction of distant metastases for patients suffering from breast cancer.
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