In Journal of translational medicine
BACKGROUND : Positron Emission Tomography (PET) imaging with Prostate-Specific Membrane Antigen (PSMA) and Fluorodeoxyglucose (FDG) represent promising biomarkers for risk-stratification of Prostate Cancer (PCa). We verified whether the expression of genes encoding for PSMA and enzymes regulating FDG cellular uptake are independent and additive prognosticators in PCa.
METHODS : mRNA expression of genes involved in glucose metabolism and PSMA regulation obtained from primary PCa specimens were retrieved from open-source databases and analyzed using an integrative bioinformatics approach. Machine Learning (ML) techniques were used to create predictive Progression-Free Survival (PFS) models. Cellular models of primary PCa with different aggressiveness were used to compare [18F]F-PSMA-1007 and [18F]F-FDG uptake kinetics in vitro. Confocal microscopy, immunofluorescence staining, and quantification analyses were performed to assess the intracellular and cellular membrane PSMA expression.
RESULTS : ML analyses identified a predictive functional network involving four glucose metabolism-related genes: ALDOB, CTH, PARP2, and SLC2A4. By contrast, FOLH1 expression (encoding for PSMA) did not provide any additive predictive value to the model. At a cellular level, the increase in proliferation rate and migratory potential by primary PCa cells was associated with enhanced FDG uptake and decreased PSMA retention (paralleled by the preferential intracellular localization).
CONCLUSIONS : The overexpression of a functional network involving four glucose metabolism-related genes identifies a higher risk of disease progression since the earliest phases of PCa, in agreement with the acknowledged prognostic value of FDG PET imaging. By contrast, the prognostic value of PSMA PET imaging is independent of the expression of its encoding gene FOLH1. Instead, it is influenced by the protein docking to the cell membrane, regulating its accessibility to tracer binding.
Bauckneht Matteo, Marini Cecilia, Cossu Vanessa, Campi Cristina, Riondato Mattia, Bruno Silvia, Orengo Anna Maria, Vitale Francesca, Carta Sonia, Chiola Silvia, Chiesa Sabrina, Miceli Alberto, D’Amico Francesca, Fornarini Giuseppe, Terrone Carlo, Piana Michele, Morbelli Silvia, Signori Alessio, Barboro Paola, Sambuceti Gianmario
2023-Jan-04
Glucose metabolism, Positron emission tomography, Prognosis, Prostate cancer, Prostate-specific membrane antigen
