Metabolomic Profiling of Extracellular Vesicles and Alternative Normalization Methods Reveal Enriched Metabolites and Strategies to Study Prostate Cancer-Related Changes

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Puhka , M , Takatalo , M , Nordberg , M-E , Valkonen , S , Nandania , J , Aatonen , M , Yliperttula , M , Laitinen , S , Velagapudi , V , Mirtti , T , Kallioniemi , O , Rannikko , A , Siljander , P R-M & Af Hallstrom , T M 2017 , ' Metabolomic Profiling of Extracellular Vesicles and Alternative Normalization Methods Reveal Enriched Metabolites and Strategies to Study Prostate Cancer-Related Changes ' , Theranostics , vol. 7 , no. 16 , pp. 3824-3841 . https://doi.org/10.7150/thno.19890

Title: Metabolomic Profiling of Extracellular Vesicles and Alternative Normalization Methods Reveal Enriched Metabolites and Strategies to Study Prostate Cancer-Related Changes
Author: Puhka, Maija; Takatalo, Maarit; Nordberg, Maria-Elisa; Valkonen, Sami; Nandania, Jatin; Aatonen, Maria; Yliperttula, Marjo; Laitinen, Saara; Velagapudi, Vidya; Mirtti, Tuomas; Kallioniemi, Olli; Rannikko, Antti; Siljander, Pia R-M; Af Hallstrom, Taija Maria
Contributor: University of Helsinki, University of Helsinki
University of Helsinki, Faculty of Pharmacy
University of Helsinki, University of Helsinki
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Biosciences
University of Helsinki, University of Helsinki
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, University of Helsinki
University of Helsinki, Clinicum
University of Helsinki, Biosciences
University of Helsinki, University of Helsinki
Date: 2017-08-23
Language: eng
Number of pages: 18
Belongs to series: Theranostics
ISSN: 1838-7640
URI: http://hdl.handle.net/10138/224629
Abstract: Body fluids are a rich source of extracellular vesicles (EVs), which carry cargo derived from the secreting cells. So far, biomarkers for pathological conditions have been mainly searched from their protein, (mi) RNA, DNA and lipid cargo. Here, we explored the small molecule metabolites from urinary and platelet EVs relative to their matched source samples. As a proof-of-concept study of intra-EV metabolites, we compared alternative normalization methods to profile urinary EVs from prostate cancer patients before and after prostatectomy and from healthy controls. Methods: We employed targeted ultra-performance liquid chromatography-tandem mass spectrometry to profile over 100 metabolites in the isolated EVs, original urine samples and platelets. We determined the enrichment of the metabolites in the EVs and analyzed their subcellular origin, pathways and relevant enzymes or transporters through data base searches. EV-and urine-derived factors and ratios between metabolites were tested for normalization of the metabolomics data. Results: Approximately 1 x 10(10) EVs were sufficient for detection of metabolite profiles from EVs. The profiles of the urinary and platelet EVs overlapped with each other and with those of the source materials, but they also contained unique metabolites. The EVs enriched a selection of cytosolic metabolites including members from the nucleotide and spermidine pathways, which linked to a number of EV-resident enzymes or transporters. Analysis of the urinary EVs from the patients indicated that the levels of glucuronate, D-ribose 5-phosphate and isobutyryl-L-carnitine were 2-26-fold lower in all pre-prostatectomy samples compared to the healthy control and post-prostatectomy samples (p <0.05). These changes were only detected from EVs by normalization to EV-derived factors or with metabolite ratios, and not from the original urine samples. Conclusions: Our results suggest that metabolite analysis of EVs from different samples is feasible using a high-throughput platform and relatively small amount of sample material. With the knowledge about the specific enrichment of metabolites and normalization methods, EV metabolomics could be used to gain novel biomarker data not revealed by the analysis of the original EV source materials.
Subject: extracellular vesicles
exosomes
metabolomics
urine
platelets
prostate cancer
HUMAN URINARY EXOSOMES
BIOMARKER DISCOVERY
HYALURONAN
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
317 Pharmacy
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