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miRNA-224 表达下调与前列腺癌的预后性能。

Downregulation and prognostic performance of microRNA 224 expression in prostate cancer.

机构信息

Department of Biochemistry and Molecular Biology, University of Athens, Athens, Greece.

出版信息

Clin Chem. 2013 Jan;59(1):261-9. doi: 10.1373/clinchem.2012.191502. Epub 2012 Nov 7.

Abstract

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(-ΔΔCq)). We performed comprehensive biostatistical analyses to explore the clinical value of miR-224 in prostate cancer.

RESULTS

miR-224 expression was significantly downregulated 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.

摘要

简介

由于广泛将前列腺特异性抗原用作前列腺癌的一般生物标志物,导致了过度诊断和过度治疗的风险。最近的研究揭示了 microRNAs(miRNAs)在前列腺癌中的巨大生物标志物潜力。本研究旨在分析与癌症相关的 miRNA(miR-224)在前列腺肿瘤中的表达模式,并探讨其临床应用价值。

方法

从 139 个前列腺组织样本中提取总 RNA。在多聚(A)聚合酶的作用下对总 RNA 进行多聚腺苷酸化后,用合适的多(T)接头合成 cDNA。通过定量实时 PCR 评估 miR-224 的表达,并通过比较定量周期法(C(q)(2(-ΔΔCq))进行分析。我们进行了全面的生物统计分析,以探讨 miR-224 在前列腺癌中的临床价值。

结果

与良性样本相比,恶性样本中 miR-224 的表达明显下调(P < 0.001)。在侵袭性较低(P = 0.017)和疾病早期阶段(P = 0.018)的前列腺肿瘤中,miR-224 的表达水平较高。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明显延长(P = 0.021)。单因素 bootstrap Cox 回归证实 miR-224 与良好的预后相关(危险比 0.314,P = 0.013);然而,调整了常规标志物的多因素分析并未将 miR-224 确定为独立的预后指标。

结论

miR-224 在前列腺癌中表达异常。通过经济有效的定量分子方法进行评估,可为前列腺癌提供有用的生物标志物。

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