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Aminopeptidase activities as prospective urinary biomarkers for bladder cancer.

ABSTRACT: Proteases have been implicated in cancer progression and invasiveness. We have investigated the activities, as opposed to simple protein levels, of selected aminopeptidases in urine specimens to serve as potential novel biomarkers for urothelial cancer.The unique urinary proteomes of males and females were profiled to establish the presence of a gender-independent set of aminopeptidases. Samples were also collected from patients with urothelial cancer and matched controls. A SOP for urine processing was developed taking into account hydration variation. Five specific aminopeptidase activity assays, using fluorophoric substrates, were optimized for evaluation of marker potential.Nineteen exopeptidases and 21 other proteases were identified in urine and the top-five most abundant aminopeptidases, identical in both genders, selected for functional studies. Depending on the enzyme, activities were consistently lower (p ? 0.05), higher or unchanged in the cancer samples as compared to controls. Two selected aminopeptidase activities used as a binary classifier resulted in a ROC curve with an AUC = 0.898.We have developed functional assays that characterize aminopeptidase activities in urine specimens with adequate technical and intraindividual reproducibility. With further testing, it could yield a reliable biomarker test for bladder cancer detection or prognostication.

SUBMITTER: Taylor JM

PROVIDER: S-EPMC4059539 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Aminopeptidase activities as prospective urinary biomarkers for bladder cancer.

Taylor Jennifer M JM Yaneva Mariana M Velasco Kevin K Philip John J Erdjument-Bromage Hediye H Ostrovnaya Irina I Lilja Hans G HG Bochner Bernard H BH Tempst Paul P

Proteomics. Clinical applications 20140331 5-6

<h4>Purpose</h4>Proteases have been implicated in cancer progression and invasiveness. We have investigated the activities, as opposed to simple protein levels, of selected aminopeptidases in urine specimens to serve as potential novel biomarkers for urothelial cancer.<h4>Experimental design</h4>The unique urinary proteomes of males and females were profiled to establish the presence of a gender-independent set of aminopeptidases. Samples were also collected from patients with urothelial cancer ...[more]

PMID: 24591208

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Project description:BackgroundBladder cancer (BC) is one of the most common malignancies globally. Early diagnosis of it can significantly improve patients' survival and quality of life. Urinary exosomes (UEs)-derived miRNAs might be a promising biomarker for BC detection.MethodA total of 12 patients with BC and 4 non-cancerous participants (as healthy control) were recruited from a single center between March 2018 and December 2019 as the discovery set. Midstream urine samples from each participants were collected and high-throughput sequencing and differentially expression analysis were conducted. Combined with miRNA expression profile of BC tissue from The Cancer Genome Atlas (TCGA), miRNAs biomarkers for BC were determined. Candidate miRNAs as biomarkers were selected followed by verification with a quantitative reverse-transcription polymerase chain reaction assay in an independent validation cohort consisting of 53 BC patients and 51 healthy controls. The receiver-operating characteristic (ROC) curve was established to evaluate the diagnostic performance of UE-derived miRNAs. The possible mechanism of miRNAs were revealed by bioinformatic analysis and explored in vitro experiments.ResultsWe identified that miR-93-5p, miR-516a-5p were simultaneously significantly increased both in UEs from BC compared with healthy control and BC tissue compared with normal tissue, which were verified by RT-qPCR in the validation cohort. Subsequently, the performance to discover BC of the miR-93-5p, miR-516a-5p was further verified with an area under ROC curve (AUC) of 0.838 and 0.790, respectively, which was significantly higher than that of urine cytology (AUC = 0.630). Moreover, miR-93-5p was significantly increased in muscle-invasive BC compared with non-muscle-invasive BC with an AUC of 0.769. Bioinformatic analysis revealed that B-cell translocation gene 2(BTG2) gene may be the hub target gene of miR-93-5p. In vitro experiments verified that miR-93-5p suppressed BTG2 expression and promoted BC cells proliferation, invasion and migration.ConclusionUrine derived exosomes have a distinct miRNA profile in BC patients, and urinary exosomal miRNAs could be used as a promising non-invasive tool to detect BC. In vitro experiments suggested that miR-93-5p overexpression may contribute to BC progression via suppressing BTG2 expression.

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Aminopeptidase activities as prospective urinary biomarkers for bladder cancer.

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Aminopeptidase activities as prospective urinary biomarkers for bladder cancer.

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