Zhang Wei, Ren Shan-Cheng, Shi Xiao-Lei, Liu Ya-Wei, Zhu Ya-Sheng, Jing Tai-Le, Wang Fu-Bo, Chen Rui, Xu Chuan-Liang, Wang Hui-Qing, Wang Hai-Feng, Wang Yan, Liu Bing, Li Yao-Ming, Fang Zi-Yu, Guo Fei, Lu Xin, Shen Dan, Gao Xu, Hou Jian-Guo, Sun Ying-Hao
Department of Urology, Changhai Hospital, The Second Military Medical University, Shanghai, P.R.China.
Prostate. 2015 May;75(6):653-61. doi: 10.1002/pros.22949. Epub 2015 Jan 18.
Long non-coding RNA (LncRNA) PCA3 has been a well-established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE).
Post-DRE first-catch urine specimens prior to prostate biopsies were prospectively collected. After the whole transcriptome amplification, quantitative real time polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels. The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA mRNA/FR0348383 mRNA × 1000). The diagnostic value of FR0348383 score was evaluated by logistic regression and decision curve analysis.
213 cases with urine samples containing sufficient mRNA were included, 94 cases had serum PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383 score was correlated with an increasing probability of a positive biopsy (P < 0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001), PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA, %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a probability threshold of 30% in the grey zone cohort, The FR0348383 score would save 52.0% of avoidable biopsies without missing any high grade cancers.
FR0348383 transcript in post-DRE urine may be a novel biomarker for detection of PCa with great diagnostic value, especially in the grey zone cohort. The application of FR0348383 score in clinical practice might avoid unnecessary prostate biopsies and increase the specificity of PCa diagnosis.
长链非编码RNA（LncRNA）PCA3已成为检测前列腺癌（PCa）的一种成熟的尿液生物标志物。我们之前的研究表明，与匹配的良性组织相比，一种新型LncRNA FR0348383在70%以上的PCa中上调。本研究的目的是评估尿液FR0348383对因前列腺特异性抗原（PSA）升高（PSA > 4.0 ng/ml）和/或直肠指检（DRE）异常而接受前列腺活检的男性的诊断价值。
前瞻性收集前列腺活检前DRE后的首次晨尿标本。在进行全转录组扩增后，应用定量实时聚合酶链反应来定量尿液中FR0348383和PSA的水平。FR0348383评分计算为PSA与FR0348383 mRNA的比值（PSA mRNA/FR0348383 mRNA × 1000）。通过逻辑回归和决策曲线分析评估FR0348383评分的诊断价值。
纳入了213例尿液样本中含有足够mRNA的病例，94例血清PSA水平为4.0 - 10.0 ng/ml。其中72例确诊为PCa。FR0348383评分升高与活检阳性概率增加相关（P < 0.001）。多变量逻辑分析表明，FR0348383评分（P < 0.001）、PSA（P = 0.004）、年龄（P = 0.007）、前列腺体积（P < 0.001）是PCa的独立预测因素。ROC分析表明，在PSA处于灰色区域的患者亚组中，FR0348383评分在预测PCa方面优于PSA、游离PSA百分比和PSA密度（AUC：0.815 vs. 0.562 vs. 0.599 vs. 0.645）。在灰色区域队列中使用30%的概率阈值时，FR0348383评分可避免52.0%的不必要活检，且不会漏诊任何高级别癌症。
DRE后尿液中的FR0348383转录本可能是一种具有重要诊断价值的新型PCa检测生物标志物，尤其是在灰色区域队列中。FR0348383评分在临床实践中的应用可能避免不必要的前列腺活检，并提高PCa诊断的特异性。
