miQA novel microRNA based diagnostic and prognostic tool for prostate cancer
miQA novel microRNA based diagnostic and prognostic tool for prostate cancer
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DOI：
10.1002/ijc.27973
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发表时间：
2013-06-15
影响因子：
6.4
通讯作者：
Ceder, Yvonne
中科院分区：
文献类型：
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作者：
Larne, Olivia;Martens-Uzunova, Elena;Ceder, Yvonne
今天，大多数前列腺肿瘤在早期阶段被发现，预后不确定。因此，我们着手鉴定具有侵袭性进展特征的前列腺癌的早期预测标志物。我们使用qRT-PCR在福尔马林固定和石蜡包埋的前列腺组织样本中测量microRNA（miRNA）的表达，这些样本来自瑞典队列的49名前列腺癌患者和25名非癌症患者，并发现13种预选的miRNA中有7种可以区分两组。随后，将四种区分性miRNA组合成配额，表示为miRNA索引引用（miQ）;（（miR-96- 5 p x miR-183- 5 p）/（miR-145- 5 p x miR 221 - 5 p））。使用引用的优点是增加了区分度，不需要内务管理，最重要的是，考虑到疾病的异质性，这可能是一个优势。发现miQ以高准确度（曲线下面积，AUC = 0.931）成功预测诊断（p < 0.0001），这在独立的荷兰队列和三个外部队列中得到验证，并且显著优于前列腺特异性抗原。重要的是，miQ还具有预测肿瘤侵袭性（AUC = 0.895）、转移性状态（AUC = 0.827）和总生存期（p = 0.0013，Wilcoxon检验HR = 6.5，中位生存期2年与5年）的预后能力，在荷兰队列中得到验证。在这项初步研究中，我们提出miQ有可能用作前列腺癌诊断的临床工具和疾病进展的预后标志物。
Today, the majority of prostate tumors are detected at early stages with uncertain prognosis. Therefore, we set out to identify early predictive markers of prostate cancer with aggressive progression characteristics. We measured the expression of microRNAs (miRNA) using qRT-PCR in formalin fixed and paraffin embedded prostatic tissue samples from a Swedish cohort of 49 patients with prostate cancer and 25 without cancer and found seven of 13 preselected miRNAs to discriminate between the two groups. Subsequently, four discriminatory miRNAs were combined to a quota, denoted the miRNA index quote (miQ); ((miR-96-5p x miR-183-5p)/(miR-145-5p x miR221-5p)). The advantage of using a quote is increased discrimination, no need for house-keepings, and most important it may be an advantage considering the heterogeneity of the disease. miQ was found to successfully predict diagnosis (p < 0.0001) with high accuracy (area under the curve, AUC = 0.931) that was verified in an independent Dutch cohort and three external cohorts, and significantly outperforming prostate-specific antigen. Importantly, miQ also has prognostic power to predict aggressiveness of tumors (AUC = 0.895), metastatic statues (AUC = 0.827) and overall survival (p = 0.0013, Wilcoxon test HR = 6.5, median survival 2 vs. 5 years), verified in the Dutch cohort. In this preliminary study, we propose that miQ has potential to be used as a clinical tool for prostate cancer diagnosis and as a prognostic marker of disease progression.