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

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

doi:10.18632/oncotarget.2691

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.

Highlights

Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the United States, with an estimated 238,599 new cases and 29,720 deaths in the year 2013 [1]
We showed that a circulating metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) fragment (MD-miniRNA) outperformed prostate-specific antigen (PSA) in predicting prostate biopsy outcomes, suggesting that MALAT-1 may be a promising biomarker for diagnosing PCa
The current standard approach to diagnose PCa is prostate biopsy, which is mostly based on elevated PSA and/or abnormal digital rectal examination (DRE)

Summary

Introduction

Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the United States, with an estimated 238,599 new cases and 29,720 deaths in the year 2013 [1]. Patients with early stage PCa can survive more than 10 years after diagnosis. The wide use of prostate-specific antigen (PSA) has greatly improved the early diagnosis of clinically localized PCa [4], resulting in a significant decrease in PCa-specific death [5]. Men with elevated serum PSA are recommended to undergo a biopsy for a definitive diagnosis. There is an urgent need to develop more sensitive, specific biomarkers to diagnose PCa at an early stage while avoiding unnecessary biopsies. As prostate cells can be detected in the urine of men after a digital rectal examination (DRE), urine-based diagnostic tests have the advantage of being non-invasive or minimally invasive. The Progensa PCA3 test has been approved by the US Food and Drug Administration and is commercially available to guide repeat biopsy decision-making

Methods

Results

Conclusion