揭示膀胱癌患者 miR-182、miR-205、miR-27a 和 miR-369 的表达模式及其临床意义。
Uncovering the expression patterns and the clinical significance of miR-182, miR-205, miR-27a and miR-369 in patients with urinary bladder cancer.
机构信息
Laboratory of proteins engineering and bioactive molecules (LIP-MB), INSAT, University of Tunis Carthage, Tunis, Tunisia.
UOSD SAFU, Department of Research, Diagnosis and Innovative Technologies, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.
出版信息
Mol Biol Rep. 2020 Nov;47(11):8819-8830. doi: 10.1007/s11033-020-05932-3. Epub 2020 Oct 31.
BACKGROUND
Given the high recurrence and progression rates and the absence of reliable markers for early detection and prognosis prediction of patients with urothelial bladder cancer (BCa), the exploration of new biomarkers with high specificity is imperative. Mainly, microRNAs (miRNAs), which are involved in the initiation and the progression of BCa. Herein, the expression patterns of miR-182, miR-205, miR-27a and miR-369 were evaluated in patients with urothelial BCa.
METHODS AND RESULTS
The expression levels of the miRNAs were investigated in 90 FFPE tissue samples (23 LG NMIBC, 44 HG NMIBC, 23 MIBC) and 10 non tumoral bladder tissues using TaqMan based RT-qPCR. Data analysis was performed using 2 method. Correlation to clinical characteristics of the patients was performed using descriptive statistics and the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of all miRNAs. MiR-27a, miR-205 and miR-369 were down-regulated whereas miR-182 was up-regulated in patients compared to controls (p < 0.001). MiR-205 and miR-182 positively segregate between NMIBC and MIBC (p = 0.002 and p = 0.000 respectively) whereas the distribution of miR-27a's expression among these tumor groups was almost significant (p = 0.05) and that of miR-369's expression was irrelevant (p = 0.618). Interestingly, miR-182 was discriminative between LG NMIBC and HG NMIBC (p < 0.001) and Ta/T1 tumors (p = 0.000). Furthermore, high levels of miR-182 were potentially predictive of progression in NMIBC patients (p = 0.01).
CONCLUSION
Collectively, a selection of miRNAs was found to be aberrantly expressed in BCa suggesting a potential diagnostic value in BCa. In addition, the clinical value of miR-182 and miR-205 as potential prognosis biomarkers was highlighted. Indeed, our data provide additional insights into cancer biology. Further functional or target studies are mandatory to strengthen these findings.
背景
鉴于尿路上皮膀胱癌（BCa）患者的高复发和高进展率，以及缺乏可靠的早期检测和预后预测标志物，探索具有高特异性的新生物标志物势在必行。主要是 microRNAs（miRNAs），它们参与了 BCa 的发生和进展。在此，评估了 miR-182、miR-205、miR-27a 和 miR-369 在尿路上皮 BCa 患者中的表达模式。
方法和结果
使用 TaqMan 基于 RT-qPCR 在 90 个 FFPE 组织样本（23 个 LG NMIBC、44 个 HG NMIBC、23 个 MIBC）和 10 个非肿瘤膀胱组织中检测了 miRNA 的表达水平。使用描述性统计和接收者操作特征（ROC）曲线分析数据。使用 2 种方法对患者的临床特征进行相关性分析。miR-27a、miR-205 和 miR-369 在患者中相对于对照下调，而 miR-182 上调（p<0.001）。miR-205 和 miR-182 在 NMIBC 和 MIBC 之间呈正分离（p=0.002 和 p=0.000 分别），而 miR-27a 的表达在这些肿瘤组之间的分布几乎显著（p=0.05），miR-369 的表达无关（p=0.618）。有趣的是，miR-182 在 LG NMIBC 和 HG NMIBC（p<0.001）和 Ta/T1 肿瘤（p=0.000）之间具有鉴别能力。此外，miR-182 高水平可能预测 NMIBC 患者的进展（p=0.01）。
结论
总之，研究发现一组 miRNA 在 BCa 中异常表达，提示其在 BCa 中具有潜在的诊断价值。此外，还强调了 miR-182 和 miR-205 作为潜在预后生物标志物的临床价值。事实上，我们的数据为癌症生物学提供了更多的见解。进一步的功能或靶标研究是必要的，以加强这些发现。
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