Elevated serum microRNA levels associate with absence of high-grade prostate cancer in a retrospective cohort.
Elevated serum microRNA levels associate with absence of high-grade prostate cancer in a retrospective cohort.
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DOI：
10.1371/journal.pone.0124245
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Nonn L
中科院分区：
文献类型：
--
作者：
Mihelich BL;Maranville JC;Nolley R;Peehl DM;Nonn L
为了减少对惰性前列腺癌（PCa）的治疗，需要生物标志物来改善对具有侵袭性疾病低风险的患者的识别。这些患者的过度治疗是因为基于活检的整个肿瘤的侵袭性的不确定性，活检不能准确地对多灶性肿瘤进行采样。循环microRNA（miRNA）是稳定的血清标志物，在PCa男性中存在差异miRNA水平。本研究的目的是鉴定与侵袭性或惰性PCa相关的循环miRNA。我们在手术前测量了150名患者的循环miRNA，并将miRNA水平与整个根治性直肠癌切除术标本的病理学进行了比较。在这项研究中，我们使用了一个非常好的特征队列的患者谁有良性前列腺增生（BPH），低级别或高级别PCa。低级别定义为通过逐步切片确定的100% Gleason 3级肿瘤的患者。高级别PCa患者的肿瘤中有30 - 90%的Gleason 4 + 5级。BPH患者至少有两次活检PCa阴性。选择21种miRNA进行分析。通过RT-qPCR定量miRNA并通过逻辑回归分析。高水平的14种miRNAs仅存在于低级别PCa或BPH患者的血清中，而高级别PCa患者的血清水平始终较低。将14种miRNA的表达水平组合成"miR评分"，其具有0.939的阴性预测值（NPV）以预测PCa和BPH患者中不存在高级别PCa。PCa患者的生化复发（BCR）是已知的，并且组合的"miR风险评分"准确地将具有低BCR风险的患者亚组分类（NPV 0.941）。总之，血清miRNAs的测量与临床风险计算器相结合可能具有术前实用性，以识别具有低风险的侵袭性PCa患者。
To reduce treatment of indolent prostate cancer (PCa), biomarkers are needed to improve identification of patients with a low-risk of having aggressive disease. Over-treatment of these patients occurs because of uncertainty in the aggressiveness of the entire tumor based on the biopsies, which do not accurately sample multifocal tumors. Circulating microRNAs (miRNAs) are stable serum markers and differential miRNA levels occur in men with PCa. The goal of this study was to identify circulating miRNAs that were associated with aggressive or indolent PCa. We measured circulating miRNAs in 150 patients prior to surgery and compared the miRNA levels to the pathology of the entire radical prostatectomy specimen. For this study we used an exceptionally well-characterized cohort of patients who had benign prostatic hyperplasia (BPH), low-grade or high-grade PCa. Low-grade was defined as patients with 100% Gleason grade 3 tumor as determined by step-wise sectioning. High-grade PCa patients had 30-90% Gleason grade 4+5 in the tumor. BPH patients had at least two biopsies negative for PCa. Twenty one miRNAs were selected for analysis. The miRNAs were quantified by RT-qPCR and analyzed by logistic regression. High levels of 14 miRNAs were exclusively present in the serum from patients with low-grade PCa or BPH, compared to men with high-grade PCa who had consistently low levels. The expression levels of the 14 miRNAs were combined into a “miR Score” which had a negative predictive value (NPV) of 0.939 to predict absence of high-grade PCa among PCa and BPH patients. Biochemical recurrence (BCR) was known for the PCa patients and a combined “miR Risk Score” accurately classified a subset of patients with low risk of BCR (NPV 0.941). In summary, measurement of serum miRNAs may have pre-surgical utility in combination with clinical risk calculators to identify patients with low risk of harboring aggressive PCa.
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影响因子：
11.2
作者：
Moltzahn F;Olshen AB;Baehner L;Peek A;Fong L;Stöppler H;Simko J;Hilton JF;Carroll P;Blelloch R
通讯作者：
Blelloch R
影响因子：
7.4
作者：
Redova M;Poprach A;Nekvindova J;Iliev R;Radova L;Lakomy R;Svoboda M;Vyzula R;Slaby O
通讯作者：
Slaby O
影响因子：
5.9
作者：
McCann, Mark J.;Rowland, Ian R.;Roy, Nicole C.
通讯作者：
Roy, Nicole C.
影响因子：
6.4
作者：
Brase, Jan C.;Johannes, Marc;Sueltmann, Holger
通讯作者：
Sueltmann, Holger
影响因子：
8.8
作者：
Bryant, R. J.;Pawlowski, T.;Catto, J. W. F.;Marsden, G.;Vessella, R. L.;Rhees, B.;Kuslich, C.;Visakorpi, T.;Hamdy, F. C.
通讯作者：
Hamdy, F. C.