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膀胱癌患者尿中MicroRNA-146a-5p表达水平升高,经尿道切除术后降低。

Expression Level of Urinary MicroRNA-146a-5p Is Increased in Patients With Bladder Cancer and Decreased in Those After Transurethral Resection.

作者信息

Sasaki Hideo, Yoshiike Miki, Nozawa Shiari, Usuba Wataru, Katsuoka Yuichi, Aida Kouichirou, Kitajima Kazuki, Kudo Hiroya, Hoshikawa Masahiro, Yoshioka Yusuke, Kosaka Nobuyoshi, Ochiya Takahiro, Chikaraishi Tatsuya

机构信息

Department of Urology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.

Department of Urology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.

出版信息

Clin Genitourin Cancer. 2016 Oct;14(5):e493-e499. doi: 10.1016/j.clgc.2016.04.002. Epub 2016 Apr 9.

Abstract

BACKGROUND

Bladder cancer is the most prevalent malignancy involving the urinary system and exhibits a markedly high recurrence rate. Therefore, reliable and noninvasive diagnostic and surveillance methods are desperately needed.

PATIENTS AND METHODS

Candidate microRNAs (miRNAs) were selected from the miRNAs that were differentially expressed in bladder cancer cell lines (T24 and RT4) compared to normal ureteral epithelial tissue using miRNA-microarray analysis. The candidate miRNAs were validated by quantitative reverse transcription polymerase chain reaction assay using voided urine samples.

RESULTS

We identified 3 miRNAs (miR-301b, -563, and -146a-5p) that demonstrated > 2-fold higher expression levels in cancer cell lines than in the normal ureteral epithelial tissue. Of these, only miR-146a-5p was consistently and significantly higher in urine samples from the patients with bladder cancer than in those from the normal individuals (P = .0014). The patients with high-grade tumors exhibited significantly higher urinary miR-146a-5p levels than those with low-grade tumors, and the patients with invasive tumors tended to show higher urinary miR-146a-5p levels than those with noninvasive tumors. Elevated urinary miR-146a-5p levels in patients with bladder cancer were decreased to the normal level after transurethral resection of the tumors (P = .0214).

CONCLUSION

Our study suggested that urinary miR-146a-5p might be useful as a new noninvasive diagnostic marker, therapeutic target, or anticancer agent for bladder cancer, as well as for increasing our understanding of cancer biology.

摘要

背景

膀胱癌是泌尿系统中最常见的恶性肿瘤,复发率极高。因此,迫切需要可靠的非侵入性诊断和监测方法。

患者与方法

通过miRNA芯片分析,从与正常输尿管上皮组织相比在膀胱癌细胞系(T24和RT4)中差异表达的miRNA中筛选候选miRNA。使用晨尿样本通过定量逆转录聚合酶链反应分析对候选miRNA进行验证。

结果

我们鉴定出3种miRNA(miR-301b、-563和-146a-5p),它们在癌细胞系中的表达水平比正常输尿管上皮组织高2倍以上。其中,只有miR-146a-5p在膀胱癌患者的尿液样本中始终显著高于正常个体(P = .0014)。高级别肿瘤患者的尿液miR-146a-5p水平显著高于低级别肿瘤患者,侵袭性肿瘤患者的尿液miR-146a-5p水平往往高于非侵袭性肿瘤患者。膀胱癌患者尿液中升高的miR-146a-5p水平在经尿道肿瘤切除后降至正常水平(P = .0214)。

结论

我们的研究表明,尿液miR-146a-5p可能作为膀胱癌的一种新的非侵入性诊断标志物、治疗靶点或抗癌药物,也有助于增进我们对癌症生物学的理解。

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