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循环外泌体微小RNA-21作为结直肠癌各肿瘤分期的生物标志物

Circulating Exosomal MicroRNA-21 as a Biomarker in Each Tumor Stage of Colorectal Cancer.

作者信息

Tsukamoto Mitsuo, Iinuma Hisae, Yagi Takahiro, Matsuda Keiji, Hashiguchi Yojiro

机构信息

Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.

出版信息

Oncology. 2017;92(6):360-370. doi: 10.1159/000463387. Epub 2017 Apr 5.

Abstract

OBJECTIVE

We clarified the predictive and prognostic value of circulating plasma exosomal microRNA-21 (miR-21) in each TNM stage of colorectal cancer (CRC) patients.

METHODS

The microRNA (miRNA) profiles of the plasma exosomes, primary tumor tissues, and liver metastasis tissues from the same CRC patients were examined using a microarray. For validation analysis, the plasma exosome samples from 326 CRC patients were measured by TaqMan miRNA assays.

RESULTS

In the miRNA microarray analyses, miR-21 showed the highest upregulation in exosomes, primary tumor tissues, and liver metastasis tissues. Significant correlations were demonstrated between exosomal miR-21 and tissue miR-21 levels. As for the relationship to the pathological condition, exosomal miR-21 showed a significant association with liver metastasis and TNM stage. The overall survival (OS) rates and disease-free survival (DFS) rates in high-exosomal-miR-21 patients were significantly worse than those in low-miR-21 patients. Exosomal miR-21 levels were an independent prognostic factor for OS and DFS in CRC patients with TNM stage II or III, and for OS in patients with TNM stage IV.

CONCLUSION

Plasma exosomal miR-21 levels are a useful biomarker for the prediction of recurrence and poor prognosis in CRC patients with TNM stage II, III, or IV.

摘要

目的

我们阐明了循环血浆外泌体微小RNA-21(miR-21)在结直肠癌(CRC)患者各TNM分期中的预测和预后价值。

方法

使用微阵列检测同一CRC患者的血浆外泌体、原发性肿瘤组织和肝转移组织的微小RNA(miRNA)谱。为进行验证分析,采用TaqMan miRNA检测法对326例CRC患者的血浆外泌体样本进行检测。

结果

在miRNA微阵列分析中,miR-21在外泌体、原发性肿瘤组织和肝转移组织中上调最为明显。外泌体miR-21与组织miR-21水平之间存在显著相关性。就与病理状况的关系而言,外泌体miR-21与肝转移和TNM分期显著相关。外泌体miR-21水平高的患者的总生存期(OS)率和无病生存期(DFS)率显著低于miR-21水平低的患者。外泌体miR-21水平是TNM II期或III期CRC患者OS和DFS以及TNM IV期患者OS的独立预后因素。

结论

血浆外泌体miR-21水平是预测TNM II期、III期或IV期CRC患者复发和预后不良的有用生物标志物。

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