新型尿液生物标志物lncRNA546用于提高前列腺特异性抗原（PSA）灰色区间前列腺癌诊断特异性的评估及多机构验证
Evaluation and multi-institutional validation of a novel urine biomarker lncRNA546 to improve the diagnostic specificity of prostate cancer in PSA gray-zone.
作者信息
Liu Fei, Shi Xiaolei, Wang Fangming, Han Sujun, Chen Dong, Gao Xu, Wang Linhui, Wei Qiang, Xing Nianzeng, Ren Shancheng
机构信息
Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Urology, Shanghai Changhai Hospital, Shanghai, China.
出版信息
Front Oncol. 2022 Aug 12;12:946060. doi: 10.3389/fonc.2022.946060. eCollection 2022.
BACKGROUND AND OBJECTIVES
Prostate specific antigen (PSA) is currently the most commonly used biomarker for prostate cancer diagnosis. However, when PSA is in the gray area of 4-10 ng/ml, the diagnostic specificity of prostate cancer is extremely low, leading to overdiagnosis in many clinically false-positive patients. This study was trying to discover and evaluate a novel urine biomarker long non-coding RNA (lncRNA546) to improve the diagnostic accuracy of prostate cancer in PSA gray-zone.
METHODS
A cohort study including consecutive 440 participants with suspected prostate cancer was retrospectively conducted in multi-urology centers. LncRNA546 scores were calculated with quantitative real-time polymerase chain reaction. The area under the receiver operating characteristic curve (AUROC), decision curve analysis (DCA) and a biopsy-specific nomogram were utilized to evaluate the potential for clinical application. Logistic regression model was constructed to confirm the predictive power of lncRNA546.
RESULTS
LncRNA546 scores were sufficient to discriminate positive and negative biopsies. ROC analysis showed a higher AUC for lncRNA546 scores than prostate cancer antigen 3 (PCA3) scores (0.78 vs. 0.66, p<0.01) in the overall cohort. More importantly, the AUC of lncRNA546 (0.80) was significantly higher than the AUCs of total PSA (0.57, p=0.02), percentage of free PSA (%fPSA) (0.64, p=0.04) and PCA3 (0.63, p<0.01) in the PSA 4-10 ng/ml cohort. A base model constructed by multiple logistic regression analysis plus lncRNA546 scores improved the predictive accuracy (PA) from 79.8% to 86.3% and improved AUC results from 0.862 to 0.915. DCA showed that the base model plus lncRNA546 displayed greater net benefit at threshold probabilities beyond 15% in the PSA 4-10 ng/ml cohort.
CONCLUSION
LncRNA546 is a promising novel biomarker for the early detection of prostate cancer, especially in the PSA 4-10 ng/ml cohort.
背景与目的
前列腺特异性抗原（PSA）是目前前列腺癌诊断中最常用的生物标志物。然而，当PSA处于4-10 ng/ml的灰色区域时，前列腺癌的诊断特异性极低，导致许多临床假阳性患者被过度诊断。本研究旨在发现并评估一种新型尿液生物标志物长链非编码RNA（lncRNA546），以提高PSA灰色区域前列腺癌的诊断准确性。
方法
在多个泌尿外科中心进行了一项回顾性队列研究，纳入440例疑似前列腺癌的连续参与者。采用定量实时聚合酶链反应计算lncRNA546评分。利用受试者工作特征曲线下面积（AUROC）、决策曲线分析（DCA）和活检特异性列线图评估其临床应用潜力。构建逻辑回归模型以确认lncRNA546的预测能力。
结果
lncRNA546评分足以区分活检阳性和阴性。ROC分析显示，在整个队列中，lncRNA546评分的AUC高于前列腺癌抗原3（PCA3）评分（0.78对0.66，p<0.01）。更重要的是，在PSA 4-10 ng/ml队列中，lncRNA546的AUC（0.80）显著高于总PSA（0.57，p=0.02）、游离PSA百分比（%fPSA）（0.64，p=0.04）和PCA3（0.63，p<0.01）的AUC。由多元逻辑回归分析加lncRNA546评分构建的基础模型将预测准确性（PA）从79.8%提高到86.3%，AUC结果从0.862提高到0.915。DCA显示，在PSA 4-10 ng/ml队列中，基础模型加lncRNA546在阈值概率超过15%时显示出更大的净效益。
结论
lncRNA546是一种有前景的新型前列腺癌早期检测生物标志物，尤其是在PSA 4-10 ng/ml队列中。
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