Abstract
BackgroundThe lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management.MethodsA metabolomics approach based on GC-MS was used to investigate the performance of volatile organic compounds (VOCs) in general and, more specifically, volatile carbonyl compounds (VCCs) present in urine as potential markers for PCa detection.ResultsResults showed that PCa patients (n = 40) can be differentiated from cancer-free subjects (n = 42) based on their urinary volatile profile in both VOCs and VCCs models, unveiling significant differences in the levels of several metabolites. The models constructed were further validated using an external validation set (n = 18 PCa and n = 18 controls) to evaluate sensitivity, specificity and accuracy of the urinary volatile profile to discriminate PCa from controls. The VOCs model disclosed 78% sensitivity, 94% specificity and 86% accuracy, whereas the VCCs model achieved the same sensitivity, a specificity of 100% and an accuracy of 89%. Our findings unveil a panel of 6 volatile compounds significantly altered in PCa patients’ urine samples that was able to identify PCa, with a sensitivity of 89%, specificity of 83%, and accuracy of 86%.ConclusionsIt is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa.
Highlights
The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management
Urinary volatile profile of PCa patients vs. controls In this study, a HS-SPME/gas chromatography-mass spectrometry (GC-MS) method was employed to evaluate differences in the urinary volatile profile of PCa patients compared with controls
The QC samples were closely clustered in the principal component analysis (PCA) scores scatter plot (Fig. S1), which confirmed the analytical reproducibility of both methods
Summary
The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management. CONCLUSIONS: It is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa. Prostate cancer (PCa) ranks second in cancer incidence and fifth in mortality among men worldwide.[1] Diagnostic strategies currently available for patients with PCa rely on prostate biopsy (PB), which is an invasive, unpleasant and potentially harmful procedure, potentially missing clinically significant cancers due to tumour heterogeneity.[2] Prostate cancer detection based on serum PSA with a cut-off of 4.0 ng/ml has limited sensitivity (of 20.5%) and specificity (ranging from 51 to 91%),[3,4] and inability to differentiate aggressive from indolent PCa,[4] leading to false negatives, to overdiagnosis and consequent overtreatment.[5] The free/total serum PSA ratio (fPSA/tPSA) has been proposed as an alternative. Discovery and validation of novel PCa biomarkers with improved sensitivity, non-invasive and able to detect earlystage disease (when PCa is potentially curable) remains an important research aim
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