A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result
A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result
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DOI：
10.1038/pcan.2015.40
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发表时间：
2015-12-01
影响因子：
4.8
通讯作者：
Brown, G. A.
中科院分区：
文献类型：
--
作者：
Donovan, M. J.;Noerholm, M.;Brown, G. A.
背景技术背景：需要新的筛查方法，可以增加侵袭性（高级别，Gleason评分>= 7）前列腺癌（PCa）的预测诊断价值，以减少非侵袭性PCa患者不必要的活检。这对于PSA在2-10 ng ml（-1）范围内的可疑患者进行首次活检尤为重要。PCA 3和ERG的生物标志物，可以增加预测值PCa在尿液中，然而，与有限的实用性作为一个数字直肠exam（DRE）是requires.METHODS：首次捕获尿液样本收集在六个网站的男性计划进行前列腺活检。提取外泌体RNA，通过逆转录-定量PCR（RT-qPCR）测量ERG和PCA 3的RNA拷贝数，并计算EXO 106评分（标准化PCA 3和ERG RNA水平之和）。将性能与标准治疗（SOC; PSA、年龄、人种或家族史）参数进行比较。列联表，逻辑回归，受试者工作特征曲线和箱形图analysed.Results：在这个队列（N = 195），二分EXO 106评分表现出良好的临床表现，在预测活检结果的任何癌症和高级别的疾病。对于高级别疾病，阴性和阳性预测值分别为97.5%和34.5%。高等级与Gleason评分的区分。与不含EXO 106的SOC相比，EXO 106和SOC组合的6例（包括良性）活检结果（曲线下面积（AUC）= 0.803）显著改善（AUC = 0.6723，P = 0.0009）。EXO 106评分中位数与组织学分级相关（P < 0.001;斯皮尔曼等级顺序）。结论：一种新的分子标记（EXO 106评分）来源于非DRE尿液，对具有“灰区”血清PSA水平的男性初次活检诊断高级别PCa具有独立的阴性预测值。它在活检决策过程中的使用可能会导致临床上无意义疾病的前列腺活检减少。
BACKGROUND: New screening methods that can add predictive diagnostic value for aggressive (high-grade, Gleason score >= 7) prostate cancer (PCa) are needed to reduce unnecessary biopsies for patients with non-aggressive PCa. This is particularly important for men presenting for an initial biopsy with an equivocal PSA in the 2-10 ng ml(-1) range. PCA3 and ERG are biomarkers that can add predictive value for PCa in urine; however, with a limited utility as a digital rectal exam (DRE) is required.METHODS: First-catch urine samples were collected at six sites from men scheduled to undergo a prostate biopsy. Exosomal RNA was extracted, RNA copy numbers of ERG and PCA3 were measured by reverse transcription-quantitative PCR (RT-qPCR), and the EXO106 score (the sum of normalized PCA3 and ERG RNA levels) was computed. Performance was compared with standard of care (SOC; PSA, age, race or family history) parameters. Contingency table, logistic regression, receiver operating characteristics curve and box-plot analyses were performed.RESULTS: In this cohort (N = 195), a dichotomous EXO106 score demonstrated good clinical performance in predicting biopsy result for both any cancer and high-grade disease. For high-grade disease, the negative and positive predictive values were 97.5% and 34.5%, respectively. The discrimination between high-grade and Gleason score. 6 (including benign) biopsy results by a combination of EXO106 and SOC (area under the curve (AUC) = 0.803) was significantly improved compared with SOC without EXO106 (AUC = 0.6723, P = 0.0009). The median EXO106 score correlated (P < 0.001; Spearman's rank order) with histologic grade.CONCLUSIONS: A novel molecular signature (EXO106 score) derived from non-DRE urine demonstrated independent, negative predictive value for the diagnosis of high-grade PCa from initial biopsy for men with 'gray zone' serum PSA levels. Its use in the biopsy decision process could result in fewer prostate biopsies for clinically insignificant disease.