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非小细胞肺癌患者肺组织中甲基化状态和 RECK mRNA 表达的意义。

Significance of methylation status and the expression of RECK mRNA in lung tissue of patients with NSCLC.

机构信息

Department of Oncology and Radiotherapy, E.Benese 13, 305 99 Pilsen, Czech Republic.

出版信息

Anticancer Res. 2009 Nov;29(11):4535-9.

Abstract

OBJECTIVES

RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is a glycoprotein which negatively regulates the activity of matrix metalloproteinases (MMPs). We analyzed differences in RECK mRNA expression in histological types of non-small cell lung cancer (NSCLC) and the relationship between promoter methylation status of RECK gene, level of RECK mRNA expression and clinicopathological values of patients with NSCLC.

PATIENTS AND METHODS

Methylation status of the promoter and the expression of RECK mRNA were analyzed in paired tissue samples (tumor and control) of 50 patients with NSCLC. The methylation status of the RECK promoter was assessed using methylation-specific PCR. The level of RECK mRNA expression was measured using an RT real-time PCR method.

RESULTS

Lower expression of RECK mRNA in NSCLC tissue was recorded compared to normal tissue (p=0.0032). Significantly lower expression of RECK in squamous cell carcinoma (SCC) tissue was observed in comparison with adenocarcinoma tissue (p=0.0051). Significant differences in expression of RECK in stages IB-IIIA were found in comparison with stage IA (p=0.0455). There was a significantly lower expression of RECK mRNA in NSCLC tissue in samples with positive RECK promoter methylation status in comparison with samples with negative promoter methylation status (p=0.0400).

CONCLUSION

We showed that there were differences in expression between histological types of NSCLC (SCC, adenocarcinoma). There was a higher expression of RECK in stage IA in comparison with stages IB-IIIA. Our results indicate that RECK could be classified as a tumor suppressor gene and is an interesting target for further investigation of MMP inhibitors.

摘要

目的

富含半胱氨酸的天冬氨酸蛋白水解酶诱导蛋白(RECK)是一种糖蛋白,可负向调节基质金属蛋白酶(MMPs)的活性。我们分析了非小细胞肺癌(NSCLC)组织学类型中 RECK mRNA 表达的差异,以及 RECK 基因启动子甲基化状态、RECK mRNA 表达水平与 NSCLC 患者临床病理值之间的关系。

患者和方法

对 50 例 NSCLC 患者的配对组织样本(肿瘤和对照)进行了 RECK 启动子甲基化状态和 RECK mRNA 表达分析。使用甲基化特异性 PCR 评估 RECK 启动子的甲基化状态。使用 RT 实时 PCR 方法测量 RECK mRNA 的表达水平。

结果

与正常组织相比,NSCLC 组织中 RECK mRNA 的表达降低(p=0.0032)。与腺癌组织相比,鳞状细胞癌(SCC)组织中 RECK 的表达明显降低(p=0.0051)。与 IA 期相比,IB-IIIA 期的 RECK 表达存在显著差异(p=0.0455)。与 RECK 启动子甲基化阴性样本相比,RECK 启动子甲基化阳性样本的 NSCLC 组织中 RECK mRNA 的表达明显降低(p=0.0400)。

结论

我们表明,NSCLC(SCC、腺癌)的组织学类型之间存在表达差异。IA 期的 RECK 表达高于 IB-IIIA 期。我们的结果表明,RECK 可能被归类为肿瘤抑制基因,是进一步研究 MMP 抑制剂的一个有趣靶点。

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