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Page 10 of 12                    Ossoliński et al. J Cancer Metastasis Treat 2019;5:1  I  http://dx.doi.org/10.20517/2394-4722.2018.63

               and IF. Interestingly commercially available urine test for patients with negative DRE examination and
               modestly elevated PSA level has been developed which is based on a panel of four amino acids: sarcosine,
               alanine, glycine and glutamic acid (Prostaririx™). Accumulation of modified nucleotides in a chemical
                                                                                            [54]
               process of deamination is characteristic for cellular processes involving DNA and RNA . Deaminated
               nucleotides (such as dITP) can be incorporated into either DNA and RNA which may result in nucleic acid
                                                                                 [55]
               instability, mistranslation and strand damage which may induce cancerogenesis . In this study we observed
               elevated level of dITP in serum of patients with PCa.

               In conclusion, this study identifies comprehensive metabolomic profile of PCa. To the best of our knowledge,
               this is the first study which examined PCa IF. Moreover it combines simultaneous metabolomic analysis of
               serum, urine and IF, which gives most accurate insight into prostate cancerogenesis. Gold-nanoparticle-
               based laser MSI allowed identification of 20 metabolites which are up- and down-regulated. Identified
               metabolites mentioned in this study suggest their role in PCa pathogenesis and should be further evaluated
               in clinical trials as potential PCa biomarkers. The limitations of this study were the relatively small number
               of participants and the fact that small percentage of intensity values can be age-related for urine and plasma
               samples.


               DECLARATIONS
               Acknowledgments
               We also thank German and Polish Bruker-Daltonics for FlexImaging 4.0. Mr. Dominik Ruman is
               acknowledged for creating search engine of chemical compounds and 3D stage control program.

               Authors’ contributions
               Sample collection: Ossoliński K, Ossolińska A, Ossoliński T
               Sample processing, MS and MSI measurements: Nizioł J, RumanT, Arendowski A
               Data analysis: RumanT, Nizioł J
               Statistical analysis: Ossoliński K, Ruman T
               Analysis of medical aspects of research: Ossoliński K, Kucharz J, Wiechno P


               Availability of data and materials
               Not applicable.


               Financial support and sponsorship
               Scientific work was funded by Ministry of Science and Higher Education Republic of Poland from the
               budget for science in the years 2016-2020 as a research project within the program “Diamond Grant” (0184/
               DIA/2016/45).

               Conflicts of interest
               All authors declared that there are no conflicts of interest.

               Ethical approval and consent to participate
               The authors state that they have obtained the appropriate consent of the local bioethics commission to carry
               out the research and in addition, for investigations involving human subjects, informed consent has been
               obtained from the participants involved.


               Consent for publication
               Not applicable.
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