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微小RNA加工酶DICER1 mRNA表达在结直肠癌患者中的临床病理及预后意义

Clinicopathological and prognostic significance of the microRNA processing enzyme DICER1 mRNA expression in colorectal cancer patients.

作者信息

Akahane Takuya

机构信息

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

出版信息

Mol Clin Oncol. 2013 Mar;1(2):267-273. doi: 10.3892/mco.2012.43. Epub 2012 Nov 22.

Abstract

The cytoplasmic ribonuclease DICER1 is one of the key enzymes in microRNA (miRNA) processing, essential for the production of mature miRNA. The effect of DICER1 expression in tumor cells on the prognosis of patients with several cancers has been examined with controversial results in various cancer types. In particular, the clinical significance of DICER1 expression in colorectal cancer (CRC) patients has yet to be determined. The aim of this study was to evaluate the correlation between the DICER1 mRNA levels and the clinicopathological characteristics and prognostic significance in CRC patients. Tumor and normal adjacent tumor tissues from 260 patients with CRC (Dukes' stage A: 40 cases, Dukes' B: 68 cases, Dukes' C: 88 cases and Dukes' D: 64 cases) were examined. The DICER1 mRNA levels were measured using the TaqMan real-time reverse transcription polymerase chain reaction (RT-PCR) method. The expression levels of DICER1 mRNAs showed a significant decrease in CRC tissues as compared to normal ones (P=0.039). A statistically significant association was observed between DICER1 mRNA expression and tumor size, depth of invasion, lymph node metastasis, lymphatic invasion and Dukes' stage. In Kaplan-Meier survival curve analysis, overall survival (OS) and disease-free survival (DFS) rates of patients with a low DICER1 mRNA expression were significantly worse compared to patients with a high DICER1 mRNA expression (OS P<0.001; DFS P<0.001). In the Cox multivariate analysis, DICER1 mRNA expression in CRC tissues was identified as an independent prognostic factor for OS [hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.13-0.64; P=0.001] and DFS (HR, 0.23; 95% CI, 0.10-0.48; P=0.001). This study demonstrated that a reduced DICER1 mRNA expression is associated with poor prognosis in CRC patients.

摘要

细胞质核糖核酸酶DICER1是微小RNA(miRNA)加工过程中的关键酶之一,对成熟miRNA的产生至关重要。肿瘤细胞中DICER1表达对几种癌症患者预后的影响已在多种癌症类型中进行了研究,但结果存在争议。特别是,DICER1在结直肠癌(CRC)患者中的临床意义尚未确定。本研究的目的是评估CRC患者中DICER1 mRNA水平与临床病理特征及预后意义之间的相关性。对260例CRC患者(Dukes分期A期:40例,Dukes分期B期:68例,Dukes分期C期:88例,Dukes分期D期:64例)的肿瘤组织及相邻正常肿瘤组织进行了检测。采用TaqMan实时逆转录聚合酶链反应(RT-PCR)法测定DICER1 mRNA水平。与正常组织相比,CRC组织中DICER1 mRNA水平显著降低(P=0.039)。观察到DICER1 mRNA表达与肿瘤大小、浸润深度、淋巴结转移、淋巴管浸润和Dukes分期之间存在统计学显著关联。在Kaplan-Meier生存曲线分析中,DICER1 mRNA表达低的患者的总生存期(OS)和无病生存期(DFS)率明显低于DICER1 mRNA表达高的患者(OS P<0.001;DFS P<0.001)。在Cox多因素分析中,CRC组织中DICER1 mRNA表达被确定为OS[风险比(HR),0.30;95%置信区间(CI),0.13-0.64;P=0.001]和DFS(HR,0.23;95%CI,0.10-0.48;P=0.001)的独立预后因素。本研究表明,DICER1 mRNA表达降低与CRC患者预后不良相关。

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