Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder Cancer

Abstract

Background: This study investigates the potential of purine nucleoside phosphorylase (PNP) as a biomarker and therapeutic target in muscle-invasive bladder cancer (MIBC). We aimed to explore PNP’s expression, prognostic value, and role in metabolic pathways, along with its association with gene mutations. Methods: We conducted multi-omics analyses using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other public databases to evaluate PNP expression across MIBC samples and its prognostic impact through Kaplan-Meier and Cox regression analyses. Functional enrichment and gene set variation analysis (GSVA) were performed to identify PNP-related pathways. In addition, in vitro siRNA knockdown experiments were carried out to assess PNP’s influence on MIBC cell proliferation. Results: Our findings revealed that PNP is significantly overexpressed in MIBC tissues and serves as an independent prognostic factor, correlating with poor clinical outcomes across multiple cohorts (TCGA: hazard ratio [HR] > 1.3, P 1.5, P = .07; GSE169455: HR > 2.8, P < .001). Functional enrichment analysis identified PNP’s involvement in various metabolic pathways. Furthermore, we observed a high frequency of RB1 mutations in the PNP-high expression group. Based on this observation, we hypothesize that patients harboring RB1 mutations may benefit from PNP-targeted therapy. In vitro experiments demonstrated that PNP knockdown significantly reduces MIBC cell proliferation. Conclusion: This study underscores PNP’s role as a promising biomarker and therapeutic target in MIBC.