Klinik und Poliklinik für Urologie, Universitätsklinikum Bonn, Germany.
Urology. 2011 May;77(5):1265.e9-16. doi: 10.1016/j.urology.2011.01.020.
To analyze circulating microRNAs (miRNA) in serum as non-invasive biomarker in patients with localized prostate cancer (PCA), benign prostate hyperplasia (BPH) and healthy individuals (HI).
Total RNA was isolated from serum samples and the circulating levels of different RNA species (miRNA, miR-16; small nuclear RNA, RNU1A-1; messenger RNA, HPRT1), as well as of 4 oncogenic miRNAs (miR-26a, miR-32, miR-195, miR-let7i), were determined using a quantitative real-time polymerase chain reaction. We also evaluated miRNA levels in a second cohort of 10 PCA patients in cancer/nonmalignant tissue, and pre- and post-prostatectomy serum samples.
The levels of miR-16 and RNU1A-1 were reliably measured, whereas HPRT1 levels were often below the detection limit of our assay. Circulating oncogenic miRNA levels were different, and especially the miR-26a level allowed sensitive (89%) discrimination of PCA and BPH patients at a moderate specificity (56%; area under the curve [AUC]: 0.703); the analysis of oncogenic miRNAs in combination increased the diagnostic accuracy (sensitivity: 78.4%; specificity: 66.7%; AUC: 0.758). Despite the low number of patients limiting the statistical power of the study, we observed correlations with clinical-pathologic parameters: miR-16, miR-195, and miR-26a were significantly correlated with surgical margin positivity; miR-195 and miR-let7i were significantly correlated with the Gleason score. Tissue miRNA levels were correlated with preprostatectomy miRNA levels in serum, and serum miRNA decreased after prostatectomy, thereby indicating tumor-associated release of miRNA.
Tumor-associated miRNAs in serum allow noninvasive discrimination of PCA and BPH.
分析局部前列腺癌（PCA）、良性前列腺增生（BPH）和健康个体（HI）血清中循环微小 RNA（miRNA）作为非侵入性生物标志物。
从血清样本中分离总 RNA，并使用定量实时聚合酶链反应测定不同 RNA 种类（miRNA、miR-16；小核 RNA、RNU1A-1；信使 RNA、HPRT1）以及 4 种致癌 miRNA（miR-26a、miR-32、miR-195、miR-let7i）的循环水平。我们还评估了第二个队列的 10 名 PCA 患者癌/非癌组织以及前列腺切除术前和术后血清样本中的 miRNA 水平。
miR-16 和 RNU1A-1 的水平可以可靠地测量，而 HPRT1 的水平常常低于我们检测方法的检测限。循环致癌 miRNA 水平不同，miR-26a 水平尤其能够以中等特异性（56%；曲线下面积 [AUC]：0.703）灵敏地区分 PCA 和 BPH 患者；对致癌 miRNA 的分析组合提高了诊断准确性（敏感性：78.4%；特异性：66.7%；AUC：0.758）。尽管患者数量较少限制了研究的统计效力，但我们观察到与临床病理参数的相关性：miR-16、miR-195 和 miR-26a 与手术切缘阳性显著相关；miR-195 和 miR-let7i 与 Gleason 评分显著相关。组织 miRNA 水平与前列腺切除术前血清中的 miRNA 水平相关，并且血清 miRNA 在前列腺切除术后降低，从而表明 miRNA 与肿瘤相关的释放。
血清中的肿瘤相关 miRNA 可实现 PCA 和 BPH 的非侵入性区分。
