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. 2025 Jan;48(1):153-160.
doi: 10.1007/s40618-024-02428-w. Epub 2024 Oct 1.

Measurement of PDE5 concentration in human serum: proof-of-concept and validation of methodology in control and prostate cancer patients

Giovanni Luca Gravina  1 , Eugenia Guida  2 , Maria Dri  2 , Renato Massoud  3 , Savino M Di Stasi  3 , Giorgio Fucci  3 , Andrea Sansone  4 , Susanna Dolci  2 , Emmanuele A Jannini  5   6
Affiliations

Measurement of PDE5 concentration in human serum: proof-of-concept and validation of methodology in control and prostate cancer patients

Giovanni Luca Gravina et al. J Endocrinol Invest. 2025 Jan.

Abstract

Purpose: We aimed to investigate if the type 5 phosphodiesterase (PDE5), an enzyme with cardinal biological functions in sexual and cardiovascular health, can be detected and quantited in human serum.

Methods: Blood samples were collected from control male and female subjects. PDE5 levels were measured by a specific ELISA kit. ROC curves weighted for age and serum levels of PSA (male subjects), or age (female subjects) were used to identify the predictive ability in the detection of PCa. Sensitivity, specificity, PPV and NPV values were determined for cut-off value determined during ROC curve analysis.

Results: 41 control male subjects, 18 control female subjects, and 55 consecutive subjects, of which 25 were affected by benign prostatic hypertrophy (BPH) and 30 with histologically confirmed prostate cancer (PCa), were studied. PDE5 serum levels were detectable in all subjects (range: 5 to 65 ng/ml). Analysis by MANCOVA identified a significant difference in serum PDE5 between control subjects or hyperplasia patients and PCa patients. Marginal means of serum PDE5 concentrations showed a significant difference (p < 0.001). The ROC curve demonstrated that PDE5 serum levels can predict men with or without PCa, with 0.806 AUC value (p < 0.0001). Using a 12.705 ng/ml PDE5 serum cut-off yielded sensitivity, specificity, PPV, and NPV of 83.3%, 77.27%, 62.5%, and 91.1% in detecting men with histologically proven PCa, respectively.

Conclusions: We demonstrated, for the first time, that PDE5 levels can be detected in human sera and that PCa patients have significantly higher PDE5 concentration compared to BPH patients or male and female controls. While serum PDE5 level measurement may open new research avenues, the clinical relevance of PDE5 levels in PCa patients deserves further investigation.

Keywords: Benign prostatic hyperplasia; Novel markers of disease; Phosphodiesterase type 5; Prostate cancer.

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Conflict of interest statement

Declarations. Conflict of interest: EAJ is or has been consultant and/or paid speaker for Bayer, Ibsa, Menarini, Shionogi, Sonofi, Pfizer, Viatris. AS has been consultant and/or paid speaker for Ibsa and Menarini. Informed consent: The informed consent has been provided by patients enrolled.

Figures

Fig. 1
Fig. 1
Serum level of PDE5 according to sex between male and female control subjects (M: n = 41; F: n = 18)
Fig. 2
Fig. 2
Box-and-whiskers plot of serum PDE5 values in men without urological disease (Controls, n = 41), with benign prostatic hyperplasia (BPH, n = 25) or with prostate cancer (PCa, n = 30)
Fig. 3
Fig. 3
Box-and-whiskers plot of serum PDE5 values in prostate cancer patients (PCa, n = 30) and subjects without prostate cancer (No-PCa, n = 66)
Fig. 4
Fig. 4
A: ROC Curve analysis with AUC value for discriminating men with (n = 30) or without (n = 66) prostate cancer. B: Sensitivity/specificity analysis to identify the optimal cut-off for PCa diagnosis
See this image and copyright information in PMC

References

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