A Pilot Study Exploring Paraoxonase-1 Tissue Protein Expression and Circulating Levels in Bladder Cancer

Paraoxonase-1 (PON1) is considered a liver-derived antioxidant enzyme circulating bound to high-density lipoproteins, with limited evidence of protein expression in human urothelial tissue. Its role in bladder cancer remains unexplored. Methylthioadenosine phosphorylase (MTAP), an enzyme related to tumor aggressiveness, may interact with oxidative and metabolic stress pathways relevant to tumor progression. We conducted an exploratory study integrating immunohistochemistry, serum biochemistry, and PON1 genotyping in 39 patients with low-grade (LGUC) or high-grade urothelial carcinoma (HGUC). Both PON1 and MTAP showed reduced expression in high-grade tumors, with MTAP reduction being more pronounced and consistent than that of PON1. Serum PON1 concentrations and activities were slightly reduced in HGUC compared with LGUC and controls. Genotype frequencies were similar between patients and controls, and polymorphisms influenced serum enzymatic activity similarly in both groups. Correlations between tissue and serum PON1 did not reach significance, although descriptively low tissue expression aligned with low serum levels. This study provides initial evidence of intratumoral PON1 expression in bladder cancer and suggests that combined PON1/MTAP immunohistochemical assessment may reflect tumor grade and biological behavior. Larger functional studies are needed to clarify their mechanistic and clinical relevance.