Downregulation and Prognostic Performance of MicroRNA 224 Expression in Prostate Cancer
Downregulation and Prognostic Performance of MicroRNA 224 Expression in Prostate Cancer
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DOI：
10.1373/clinchem.2012.191502
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发表时间：
2013-01-01
影响因子：
9.3
通讯作者：
Scorilas, Andreas
中科院分区：
文献类型：
--
作者：
Mavridis, Konstantinos;Stravodimos, Konstantinos;Scorilas, Andreas
简介：前列腺特异性抗原作为一种通用的前列腺癌生物标志物的广泛使用带来了过度诊断和过度治疗的危险。最近的研究揭示了microRNA（miRNAs）在前列腺癌中的巨大生物标志物能力。本研究的目的是分析miR-224（一种与癌症相关的miRNA）在前列腺肿瘤中的表达模式，并探讨其临床应用价值。总RNA经poly（A）聚合酶多聚腺苷酸化后，用合适的poly（T）接头合成cDNA。通过定量实时PCR评估miR-224表达，并使用比较定量循环方法C-q（2-（Delta Delta Cq））进行分析。结果：miR-224在前列腺癌组织中的表达显著低于良性前列腺癌组织（P < 0.001）。在侵袭性较低（P = 0.017）和疾病早期（P = 0.018）的前列腺肿瘤中发现了较高的miR-224表达水平。与miR-224阴性患者相比，miR-224阳性的前列腺癌患者的无进展生存期显著延长（P = 0.021）。单变量bootstrap考克斯回归证实miR-224与良好的预后相关（风险比0.314，P = 0.013）;然而，多变量分析，调整传统标记物，并没有将miR-224确定为独立的预后指标。通过经济有效的定量分子方法对其进行评估，可以为前列腺癌提供有用的生物标志物。(C)2012年美国临床化学协会
INTRODUCTION: The extensive use of prostate-specific antigen as a general prostate cancer biomarker has introduced the hazards of overdiagnosis and overtreatment. Recent studies have revealed the immense biomarker capacity of microRNAs (miRNAs) in prostate cancer. The aim of this study was to analyze the expression pattern of miR-224, a cancer-related miRNA, in prostate tumors and investigate its clinical utility.METHODS: Total RNA was isolated from 139 prostate tissue samples. After the polyadenylation of total RNA by poly(A) polymerase, cDNA was synthesized with a suitable poly(T) adapter. miR-224 expression was assessed by quantitative real-time PCR and analyzed with the comparative quantification cycle method, C-q(2-(Delta Delta Cq)). We performed comprehensive biostatistical analyses to explore the clinical value of miR-224 in prostate cancer.RESULTS: miR-224 expression was significantly down-regulated in malignant samples compared with benign samples (P < 0.001). Higher miR-224 expression levels were found in prostate tumors that were less aggressive (P = 0.017) and in an earlier disease stage (P = 0.018). Patients with prostate cancer who were positive for miR-224 had significantly enhanced progression-free survival intervals compared with miR-224 negative patients (P = 0.021). Univariate bootstrap Cox regression confirmed that miR-224 was associated with favorable prognosis (hazard ratio 0.314, P = 0.013); nonetheless, multivariate analysis, adjusted for conventional markers, did not identify miR-224 as an independent prognostic indicator.CONCLUSIONS: miR-224 is aberrantly expressed in prostate cancer. Its assessment by cost-effective quantitative molecular methodologies could provide a useful biomarker for prostate cancer. (C) 2012 American Association for Clinical Chemistry