Assessment of nucleosides as putative tumor biomarkers in prostate cancer screening by CE-UV.
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.
Department of Analytical Chemistry, Institute of Chemistry, University of Campinas, P.O. Box 6154, 13083-970, Campinas, São Paulo, Brazil.
Adriana Zardini
AZ
Buzatto
Department of Analytical Chemistry, Institute of Chemistry, University of Campinas, P.O. Box 6154, 13083-970, Campinas, São Paulo, Brazil.
Mariana
M
de Oliveira Silva
Department of Analytical Chemistry, Institute of Chemistry, University of Campinas, P.O. Box 6154, 13083-970, Campinas, São Paulo, Brazil.|National Institute of Science and Technology for Bioanalytics, Institute of Chemistry, University of Campinas, P.O. Box 6154, 13083-970, Campinas, São Paulo, Brazil.
Ronei Jesus
RJ
Poppi
Department of Analytical Chemistry, Institute of Chemistry, University of Campinas, P.O. Box 6154, 13083-970, Campinas, São Paulo, Brazil. avsimionato@iqm.unicamp.br.|National Institute of Science and Technology for Bioanalytics, Institute of Chemistry, University of Campinas, P.O. Box 6154, 13083-970, Campinas, São Paulo, Brazil. avsimionato@iqm.unicamp.br.
Ana Valéria Colnaghi
AVC
Simionato
D014408:Biomarkers, Tumor; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009705:Nucleosides / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
D014408:Biomarkers, Tumor; D009705:Nucleosides
Blood serum; Carcinogenesis; Micellar electrokinetic capillary chromatography,·Tumor biomarker; Nucleosides; Prostate cancer; Target metabolome