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胃癌中 microRNA-107 及其与 DICER1 mRNA 表达的临床病理及预后意义。

Clinicopathological and prognostic significance of microRNA-107 and its relationship to DICER1 mRNA expression in gastric cancer.

机构信息

Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan.

出版信息

Oncol Rep. 2012 Jun;27(6):1759-64. doi: 10.3892/or.2012.1709. Epub 2012 Mar 7.

DOI:10.3892/or.2012.1709
PMID:22407237
Abstract

microRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression. It is known that miRNA-107 (miR-107) promotes cancer invasion and metastasis. However, the relationship between clinicopathological factors and the prognostic significance of miR-107 for gastric cancer patients remains elusive. In this study, we evaluated the prognostic value of miR-107 using tissue samples from gastric cancer patients. Furthermore, the relationship between miR-107 and the mRNA levels of its target gene DICER1 was examined. The expression levels of miR-107 and DICER1 mRNA in tumor tissues and adjacent normal tissues of 161 gastric cancer patients were examined (TNM stage I, 29 patients; stage II, 31 patients; stage III, 51 patients and stage IV, 50 patients). miR-107 levels were measured by Taqman microRNA assays, and DICER1 mRNA levels were measured by the Taqman real-time RT-PCR method. In the analysis by real-time PCR-based miRNA arrays using pooled RNA samples from five gastric cancer patients, expression of miR-107, miR-21, miR-196a, miR-26b, miR-9, miR-142-3p, miR-30b, miR-150, miR-191 and miR-17 was found to be upregulation. The mean expression level of miR-107 was significantly higher in the tumor tissues compared to that of normal tissues. In the comparison of clinicopathological factors, miR-107 expression showed significant association with depth of tumor invasion, lymph node metastasis and stage. In Kaplan-Meier survival curve analysis, overall survival rates (OS) and disease-free survival rates (DFS) of patients with high miR-107 expression were significantly worse than those of patients with low miR-107 expression. In the Cox multivariate analysis, it was shown that miR-107 expression in gastric cancer tissues was an independent prognostic factor for OS and DFS. Significant inverse correlations were demonstrated between miR-107 and DICER1 mRNA. Our results indicate that miR-107 may be useful as an effective biomarker for prediction of a poor prognosis in gastric cancer patients.

摘要

微小 RNA(miRNA)是一种调节靶基因表达的小非编码 RNA。已知 miRNA-107(miR-107)可促进癌症侵袭和转移。然而,miR-107 与胃癌患者临床病理因素之间的关系及其对预后的意义仍不清楚。在本研究中,我们使用胃癌患者的组织样本评估了 miR-107 的预后价值。此外,还研究了 miR-107 与其靶基因 DICER1 的 mRNA 水平之间的关系。检测了 161 例胃癌患者肿瘤组织和癌旁正常组织中 miR-107 和 DICER1 mRNA 的表达水平(TNM 分期 I 期 29 例,II 期 31 例,III 期 51 例,IV 期 50 例)。采用 Taqman 微 RNA 检测试剂盒检测 miR-107 水平,采用 Taqman 实时 RT-PCR 法检测 DICER1 mRNA 水平。在对 5 例胃癌患者的混合 RNA 样本进行基于实时 PCR 的 miRNA 阵列分析时,发现 miR-107、miR-21、miR-196a、miR-26b、miR-9、miR-142-3p、miR-30b、miR-150、miR-191 和 miR-17 的表达上调。与正常组织相比,肿瘤组织中 miR-107 的平均表达水平明显升高。在与临床病理因素的比较中,miR-107 的表达与肿瘤浸润深度、淋巴结转移和分期显著相关。在 Kaplan-Meier 生存曲线分析中,高 miR-107 表达患者的总生存率(OS)和无病生存率(DFS)明显低于低 miR-107 表达患者。在 Cox 多因素分析中,胃癌组织中 miR-107 的表达是 OS 和 DFS 的独立预后因素。miR-107 与 DICER1 mRNA 之间存在显著的负相关关系。我们的研究结果表明,miR-107 可能是预测胃癌患者不良预后的有效生物标志物。

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