Analytical and Bioanalytical Chemistry

, Volume 409, Issue 13, pp 3289–3297 | Cite as

Assessment of nucleosides as putative tumor biomarkers in prostate cancer screening by CE–UV

  • Adriana Zardini Buzatto
  • Mariana de Oliveira Silva
  • Ronei Jesus Poppi
  • Ana Valéria Colnaghi Simionato
Paper in Forefront
First Online:
Received:
Revised:
Accepted:

Abstract

Cancer is responsible for millions of deaths worldwide, but most base diseases may be cured if detected early. Screening tests may be used to identify early-stage malignant neoplasms. However, the major screening tool for prostate cancer, the prostate-specific antigen test, has unsuitable sensitivity. Since cancer cells may affect the pattern of consumption and excretion of nucleosides, such biomolecules are putative biomarkers that can be used for diagnosis and treatment evaluation. Using a previously validated method for the analysis of nucleosides in blood serum by capillary electrophoresis with UV–vis spectroscopy detection, we investigated 60 samples from healthy individuals and 42 samples from prostate cancer patients. The concentrations of nucleosides in both groups were compared and a multivariate partial least squares–discriminant analysis classification model was optimized for prediction of prostate cancer. The validation of the model with an independent sample set resulted in the correct classification of 82.4% of the samples, with sensitivity of 90.5% and specificity of 76.7%. A significant downregulation of 5-methyluridine and inosine was observed, which can be indicative of the carcinogenic process. Therefore, such analytes are potential candidates for prostate cancer screening.

Graphical Abstract

Separation of the studied nucleosides and the internal standard 8-Bromoguanosine by CE-UV (a); classification of the external validation samples (30 from healthy volunteers and 21 from prostate cancer patients) by the developed Partial Least Square – Discriminant Analysis (PLS-DA) model with accuracy of 82.4% (b); Receiver Operating Characteristics (ROC) curve (c); and Variable Importance in the Projection (VIP) values for the studied nucleosides (d). A significant down-regulation of 5- methyluridine (5mU) and inosine (I) was observed, which can be indicative of the presence of prostate tumors.

Keywords

Blood serum Micellar electrokinetic capillary chromatography,·Tumor biomarker Nucleosides Target metabolome Prostate cancer Carcinogenesis 
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Notes

Acknowledgments

The authors thank the Clinics Hospital Blood Center (University of Campinas) and Laurione Candido de Oliveira for providing the serum samples from prostate cancer patients, Coordination for the Improvement of Higher Education Personnel (CAPES) for a scholarship to A.Z.B, the National Council for Scientific and Technological Development (CNPq) for financial support, and São Paulo Research Foundation (FAPESP) for financial support and a scholarship for M.O.S..

Compliance with ethical standards

Conflict of interest

The authors declare they have no conflict of interest.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Ethical approval

This work does not involve any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants in the study.

Funding

This study was funded by Coordination for the Improvement of Higher Education Personnel (CAPES), the National Council for Scientific and Technological Development (CNPq), and São Paulo Research Foundation (FAPESP).

Supplementary material

216_2017_297_MOESM1_ESM.pdf (469 kb)
ESM 1 (PDF 468 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Adriana Zardini Buzatto
    • 1
  • Mariana de Oliveira Silva
    • 1
  • Ronei Jesus Poppi
    • 1
    • 2
  • Ana Valéria Colnaghi Simionato
    • 1
    • 2
  1. 1.Department of Analytical Chemistry, Institute of ChemistryUniversity of CampinasCampinasBrazil
  2. 2.National Institute of Science and Technology for Bioanalytics, Institute of ChemistryUniversity of CampinasCampinasBrazil

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