Prognostic Significance of Programmed Cell Death-1, Programmed Cell Death-Ligand 1, Programmed Cell Death-Ligand 2, and Fibroblast Growth Factor Receptor 3 mRNA Expression in Bladder Cancer

Introduction: This study aimed to evaluate the prognostic significance of programmed cell death (PD)-1/PD-ligand 1 (PD-L1), PD-ligand 2 (PD-L2), and fibroblast growth factor receptor 3 (FGFR3) expression in bladder cancer (BC). Methods: A retrospective study was conducted on BC patients who underwent transurethral resection between 2005 and 2014. Of the initial 136 patients, 31 were excluded for not meeting the inclusion criteria, leaving 105 cases for the final analysis. The mRNA levels of PD-1/PD-L1/PD-L2 and FGFR3 were assessed using quantitative reverse transcription PCR and NanoString technology. Results: High expression of PD-1 and its ligands (PD-L1/PD-L2) showed a strong correlation with each other and was associated with poor clinical outcomes, including higher tumor stage, grade, and cancer-specific mortality (p < 0.001). Conversely, high FGFR3 expression was associated with improved survival and more favorable clinicopathological features. Interestingly, an inverse relationship was observed between FGFR3 and PD-1 (p = 0.032) and PD-L1 (p = 0.016) expression. High mRNA expression profiles of PD-1, PD-L1, PD-L2, and low FGFR3 expression were associated with worse cancer-specific survival (p < 0.001). Multivariate analysis revealed that advanced stage, low FGFR3 expression, and high PD-L2 expression are independent predictors of poor prognosis in BC patients. Conclusion: Our findings suggest that elevated levels of PD-1, PD-L1, and PD-L2, combined with reduced FGFR3 expression, may assist in identifying patients with poor outcomes and highlight their potential as prognostic biomarkers in BC.