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Development and prospective multicenter evaluation of the long noncoding RNA MALAT-1 as a diagnostic urinary biomarker for prostate cancer

2014; Impact Journals LLC; Volume: 5; Issue: 22 Linguagem: Inglês

10.18632/oncotarget.2691

1949-2553

Fubo Wang, Shancheng Ren, Rui Chen, Ji Lu, Xiaolei Shi, Yasheng Zhu, Wei Zhang, Taile Jing, Chao Zhang, Jian Shen, Chuanliang Xu, Huiqing Wang, Haifeng Wang, Yang Wang, Bin Liu, Yaoming Li, Ziyu Fang, Fei Guo, Meng Qiao, Chengyao Wu, Qiang Wei, Danfeng Xu, Dan Shen, Xin Lü, Xu Gao, Jianguo Hou, Yinghao Sun,

Molecular Biology Techniques and Applications

// Fubo Wang 1,* , Shancheng Ren 1,* , Rui Chen 1,* , Ji Lu 1 , Xiaolei Shi 1 , Yasheng Zhu 1 , Wei Zhang 1 , Taile Jing 1 , Chao Zhang 1 , Jian Shen 1,2 , Chuanliang Xu 1 , Huiqing Wang 1 , Haifeng Wang 1 , Yang Wang 3 , Bin Liu 1 , Yaoming Li 1 , Ziyu Fang 1 , Fei Guo 1 , Meng Qiao 1 , Chengyao Wu 1 , Qiang Wei 4 , Danfeng Xu 5 , Dan Shen 1 , Xin Lu 1 , Xu Gao 1 , Jianguo Hou 1 and Yinghao Sun 1 1 Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China 2 Department of Urology, Changshu NO. 2 People’s Hospital, Changshu, Jiangsu Province, China 3 Department of Pathology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China 4 Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China 5 Department of Urology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China * These authors contributed equally to this work Correspondence: Yinghao Sun, email: // Keywords : prostate cancer, urine, biomarker, prostate biopsy, PSA, MALAT-1 Received : August 24, 2014 Accepted : November 04, 2014 Published : November 04, 2014 Abstract The current strategy for diagnosing prostate cancer (PCa) is mainly based on the serum prostate-specific antigen (PSA) test. However, PSA has low specificity and has led to numerous unnecessary biopsies. We evaluated the effectiveness of urinary metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a long noncoding RNA, for predicting the risk of PCa before biopsy. The MALAT-1 score was tested in a discovery phase and a multi-center validation phase. The predictive power of the MALAT-1 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. As an independent predictor of PCa, the MALAT-1 score was significantly higher in men with a positive biopsy than in those with a negative biopsy. The ROC analysis showed a higher AUC for the MALAT-1 score (0.670 and 0.742) vs. the total PSA (0.545 and 0.601) and percent free PSA (0.622 and 0.627) in patients with PSA values of 4.0-10 ng/ml. According to the decision curve analysis, using a probability threshold of 25%, the MALAT-1 model would prevent 30.2%-46.5% of unnecessary biopsies in PSA 4–10 ng/ml cohorts, without missing any high-grade cancers. Our results demonstrate that urine MALAT-1 is a promising biomarker for predicting prostate cancer risk.