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血浆微小RNA谱:鉴定miR-25作为食管鳞状细胞癌的一种新型诊断和监测生物标志物。

Plasma microRNA profiles: identification of miR-25 as a novel diagnostic and monitoring biomarker in oesophageal squamous cell carcinoma.

作者信息

Komatsu S, Ichikawa D, Hirajima S, Kawaguchi T, Miyamae M, Okajima W, Ohashi T, Arita T, Konishi H, Shiozaki A, Fujiwara H, Okamoto K, Yagi N, Otsuji E

机构信息

Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.

Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.

出版信息

Br J Cancer. 2014 Oct 14;111(8):1614-24. doi: 10.1038/bjc.2014.451. Epub 2014 Aug 12.

Abstract

BACKGROUND

Recent studies have demonstrated that microRNAs are stably detectable in plasma/serum because of their binding to specific proteins or being packaged in secretory particles. This study was designed to detect novel microRNAs in plasma for cancer detection and monitoring using microRNA array-based approaches in oesophageal squamous cell carcinoma (ESCC) patients.

METHODS

Through the integration of two Toray 3D-Gene microRNA array-based approaches to compare plasma microRNA levels between ESCC patients and healthy volunteers and between preoperative and postoperative ESCC patients, we identified a novel plasma biomarker in ESCC.

RESULTS

(1) Eight upregulated and common microRNAs (miR-15b, 16, 17, 25, 19b, 20a, 20b, and 106a) were selected using two high-resolution microRNA array approaches. (2) Test-scale analyses by quantitative RT-PCR validated a significant higher levels of plasma miR-19b (P=0.0020) and miR-25 (P=0.0030) in ESCC patients than controls. However, a significant correlation was observed between plasma miR-19b levels and concentrations of red blood cells (P=0.0073) and haemoglobin (P=0.0072). (3) miR-25 expression was found to be significantly higher in ESCC tissues (P=0.0157) and ESCC cell lines (P=0.0093) than in normal tissues and fibroblasts. (4) In a large-scale validation analysis, plasma miR-25 levels were significantly higher in 105 preoperative (P<0.0001) ESCC patients who underwent curative oesophagectomy and 20 superficial ESCC patients who underwent endoscopic resection (P<0.0001) than in 50 healthy volunteers. (5) Plasma miR-25 levels were significantly reduced in postoperative samples than in preoperative samples (P<0.0005) and were significantly increased during ESCC recurrences (P=0.0145).

CONCLUSIONS

Plasma miR-25 might be a clinically useful biomarker for cancer detection and the monitoring of tumour dynamics in ESCC patients.

摘要

背景

最近的研究表明,由于微小RNA与特定蛋白质结合或被包装在分泌颗粒中,因此在血浆/血清中可稳定检测到。本研究旨在使用基于微RNA阵列的方法检测食管癌鳞状细胞癌(ESCC)患者血浆中的新型微RNA,用于癌症检测和监测。

方法

通过整合两种基于东丽3D基因微RNA阵列的方法,比较ESCC患者与健康志愿者之间以及ESCC患者术前与术后血浆微RNA水平,我们在ESCC中鉴定出一种新型血浆生物标志物。

结果

(1)使用两种高分辨率微RNA阵列方法筛选出8种上调且常见的微RNA(miR-15b、16、17、25、19b、20a、20b和106a)。(2)通过定量RT-PCR进行的测试规模分析验证了ESCC患者血浆中miR-19b(P=0.0020)和miR-25(P=0.0030)水平显著高于对照组。然而,观察到血浆miR-19b水平与红细胞浓度(P=0.0073)和血红蛋白(P=0.0072)之间存在显著相关性。(3)发现miR-25在ESCC组织(P=0.0157)和ESCC细胞系(P=0.0093)中的表达明显高于正常组织和成纤维细胞。(4)在大规模验证分析中,105例接受根治性食管切除术的术前ESCC患者(P<0.0001)和20例接受内镜切除术的浅表ESCC患者(P<0.0001)血浆miR-25水平显著高于50名健康志愿者。(5)术后样本中血浆miR-25水平显著低于术前样本(P<0.0005),且在ESCC复发期间显著升高(P=0.0145)。

结论

血浆miR-25可能是ESCC患者癌症检测和肿瘤动态监测的一种临床有用生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c2a/4200091/a0534bf6004c/bjc2014451f1.jpg

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