Abstract
Prostate-specific antigen (PSA) is the main biomarker for the screening of prostate cancer (PCa), which has a high sensibility (higher than 80%) that is negatively offset by its poor specificity (only 30%, with the European cut-off of 4 ng/mL). This generates a large number of useless biopsies, involving both risks for the patients and costs for the national healthcare systems. Consequently, efforts were recently made to discover new biomarkers useful for PCa screening, including our proposal of interpreting a multi-parametric urinary steroidal profile with multivariate statistics. This approach has been expanded to investigate new alleged biomarkers by the application of untargeted urinary metabolomics. Urine samples from 91 patients (43 affected by PCa; 48 by benign hyperplasia) were deconjugated, extracted in both basic and acidic conditions, derivatized with different reagents, and analyzed with different gas chromatographic columns. Three-dimensional data were obtained from full-scan electron impact mass spectra. The PARADISe software, coupled with NIST libraries, was employed for the computation of PARAFAC2 models, the extraction of the significative components (alleged biomarkers), and the generation of a semiquantitative dataset. After variables selection, a partial least squares–discriminant analysis classification model was built, yielding promising performances. The selected biomarkers need further validation, possibly involving, yet again, a targeted approach.
Highlights
Prostate cancer (PCa) is the most common non-skin cancer in men [1,2] and the second most frequently diagnosed malignancy in males worldwide [3]
The first biomarker for PCa detection was prostatic acid phosphatase (PAP), which was introduced in the 1930s [1]
In the 1980s, PAP was replaced by prostate-specific antigen (PSA) [1,4], a secreted protein encoded by a prostate-specific gene and member of the tissue kallikrein family [1], which is produced almost exclusively in the prostate [5,6]
Summary
Prostate cancer (PCa) is the most common non-skin cancer in men [1,2] and the second most frequently diagnosed malignancy in males worldwide [3]. A large number of patients affected by a benign pathology, such as inflammation or hyperplasia, exhibited abnormal PSA values, which lead to the execution of useless biopsies and demonstrate the low specificity of this biomarker [1,6]. This phenomenon was generally designated as “overdiagnosis” or “overtreatment” [1,4,7,8]
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