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血浆 miR-15b-5p 和 miR-590-5p 可用于区分膀胱癌患者与健康个体。

Plasma miR‑15b‑5p and miR‑590‑5p for distinguishing patients with bladder cancer from healthy individuals.

机构信息

Department of Urology, Charité‑Universitätsmedizin Berlin, D‑10117 Berlin, Germany.

出版信息

Oncol Rep. 2019 Oct;42(4):1609-1620. doi: 10.3892/or.2019.7247. Epub 2019 Jul 24.

DOI:10.3892/or.2019.7247
PMID:31364733
Abstract

MicroRNAs (miRNAs/miRs) act as markers for various cancers, including bladder cancer (BC). Plasma miRNAs are potential biomarkers for the noninvasive diagnosis and long‑term surveillance of BC. The aim of the present study was to identify diagnostically reliable miRNAs in the plasma and examine their potential monitoring capacity. miRNAs were measured by reverse transcription‑quantitative polymerase chain reaction. The study was performed as a discovery phase, which included plasma samples from each of the 10 patients with and without BC prior to transurethral resection (TURB). The results were validated in a second phase, involving 36 patients with plasma samples collected before the second TURB or radical cystectomy (RC), and after RC. During the discovery step, three elevated miRNAs (miR‑15b‑5p, miR‑590‑5p, miR‑29b‑3p) and two decreased miRNAs (miR‑10b‑5p, miR‑144‑5p) were selected as potential miRNA candidates for further validation. miR‑15b‑5p and miR‑590‑5p were finally confirmed to discriminate between cancer cases and controls; however, for disease monitoring of BC, both miRNAs were not suitable as a decline in the miRNA levels was not observed in some patients after tumor removal. Our results suggested that circulating miR‑15b‑5p and miR‑590‑5p have useful diagnostic potential for BC, but are rather unsuitable as monitoring markers for disease. The reasons of this apparent contradictory observation may be due to the aspect of biological variation of circulating miRNAs and serial measurements could be unreliable.

摘要

微小 RNA(miRNAs/miRs)可作为多种癌症(包括膀胱癌(BC))的标志物。血浆 miRNAs 是用于 BC 非侵入性诊断和长期监测的潜在生物标志物。本研究的目的是鉴定血浆中具有诊断可靠性的 miRNA,并研究其潜在的监测能力。采用逆转录定量聚合酶链反应(qRT-PCR)检测 miRNA。该研究分为发现阶段和验证阶段。在发现阶段,纳入了 10 例经尿道膀胱肿瘤切除术(TURB)治疗的 BC 患者和 10 例非 BC 患者的血浆样本,每位患者在 TURB 治疗前均采集了一份血浆样本。在验证阶段,纳入了 36 例接受第二次 TURB 或根治性膀胱切除术(RC)治疗的患者的血浆样本,在第二次 TURB 或 RC 治疗前以及 RC 治疗后均采集了血浆样本。在发现阶段,选择了 3 个上调 miRNA(miR-15b-5p、miR-590-5p、miR-29b-3p)和 2 个下调 miRNA(miR-10b-5p、miR-144-5p)作为进一步验证的潜在 miRNA 候选物。最终,miR-15b-5p 和 miR-590-5p 被证实可用于区分癌症病例和对照组;然而,对于 BC 的疾病监测,这两种 miRNA 均不适合,因为在一些患者中,肿瘤切除后 miRNA 水平并未下降。我们的研究结果表明,循环 miR-15b-5p 和 miR-590-5p 对 BC 具有有用的诊断潜力,但作为疾病监测标志物并不合适。造成这种看似矛盾的观察结果的原因可能与循环 miRNAs 的生物学变异有关,而连续测量可能不可靠。

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