title: Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 derived miniRNA as a novel plasma-based biomarker for diagnosing prostate cancer.
abstract: Examining plasma RNA is an emerging non-invasive diagnosis technique. However, whether tumour-derived long non-coding RNAs (lncRNAs) in plasma can be used as a novel approach to detect human prostate cancer (PCa) has not yet been established. The study was divided into three parts: (1) the characteristics of PCa-related lncRNA fragments were systematically studied in the plasma or serum of 25 patients; (2) the source of the circulating lncRNA fragments was explored in vitro and in vivo; and (3) the diagnostic performance of metastasis associated in lung adenocarcinoma transcript 1 (MALAT-1) derived (MD) miniRNA was validated in an independent cohort of 192 patients. The expression levels of lncRNAs were measured by quantitative real time polymerase chain reaction (qRT-PCR). The MD-miniRNA copies were calculated using a standard curve in an area under the ROC curve (AUC)-receiver operating characteristic (ROC) analysis. Genome-wide profiling revealed that MALAT-1 and prostate cancer gene 3 (PCA3) are overexpressed in PCa tissues. Plasma lncRNAs probably exist in the form of fragments in a stable form. MD-miniRNA enters cell culture medium at measurable levels, and MD-miniRNA derived from human PCa xenografts actually enters the circulation in vivo and can be measured to distinguish xenografted mice from controls. In addition, plasma MD-miniRNA levels are significantly elevated in PCa patients compared to non-PCa patients (p<0.001). At a cut-off of 867.8 MD-miniRNA copies per microlitre of plasma, the sensitivity is 58.6%, 58.6% and 43.5% and the specificity is 84.8%, 84.8% and 81.6% for discriminating PCa from non-PCa, positive biopsy from negative biopsy and positive biopsy from negative biopsy, respectively. We conclude that MD-miniRNA can be used as a novel plasma-based biomarker for PCa detection and can improve diagnostic accuracy by predicting prostate biopsy outcomes. Further large-scale studies are needed to confirm our findings.
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China. renshancheng@gmail.com
authors.forename: Shancheng
authors.initials: S
authors.lastname: Ren
authors.forename: Fubo
authors.initials: F
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Weidong
authors.initials: W
authors.lastname: Xu
authors.forename: Ji
authors.initials: J
authors.lastname: Lu
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Xu
authors.forename: Chengyao
authors.initials: C
authors.lastname: Wu
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Hou
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001706:Biopsy; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D005260:Female; D020869:Gene Expression Profiling; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D011237:Predictive Value of Tests; D062085:RNA, Long Noncoding / Q000235:genetics*; D012334:RNA, Neoplasm / Q000097:blood*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D014183:Transplantation, Heterologous; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm; C479341:prostate cancer antigen 3, human
keywords: Biomarker; Diagnosis; Long non-coding RNA; MALAT-1; Prostate cancer