Prognostic Significance of PD-L2 Expression in Association with Neutrophil-to-Lymphocyte Ratio in Urothelial Carcinoma of the Bladder

Document Type : Research Articles


1 Division of Urology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta, Indonesia.

2 Division of Urology, Department of Surgery, Faculty of Medicine, Universitas Syiah Kuala/ dr. Zainoel Abidin General Hospital, Banda Aceh, Indonesia.


Background: The prognostic significance of tumoral programmed death-ligand 2 (PD-L2) expression in urothelial bladder cancer (UBCs) is under-investigated , although it can potentially  to become a regulatory agent of cancer immunity. In the search for supporting biomarkers, the neutrophil-to-lymphocyte ratio (NLR) as a readily available surrogate marker of immune status has been associated with clinical outcomes and other prognostic factors in various types  of cancer. Here we evaluate the prognostic ability of baseline NLR in addition to PD-L2 expression in bladder cancer. Methods: We used a retrospective cohort of UBCs patients from the authors’ institutions. We classified patients according to their PD-L2 and NLR levels. We associated the prognostic outcome of each group with disease-free survival (DFS) and overall survival (OS). Results: Thirty patients had a tumor with positive PD-L2 expression. We found no significant correlation between PD-L2 expression and NLR. PD-L2 status failed to provide a significant prognostic impact (disease-free survival [DFS] and overall survival [OS] rate at 5 years, 42.85% in PD-L2-high versus 65.75% in PD-L2-low patients; p = 0.057, 42.85% in PD-L2-high patients versus 62.5% in PD-L2-low patients; p = 0.112, respectively). NLR status also failed to exhibit a significant prognostic impact (DFS and OS rate at 5 years, 44.44% in PD-L2-high versus 66.66% in PD-L2-low patients; p = 0.232, 55.55% in PD-L2-high versus 71.43% in PD-L2-low patients; P = 0.894, respectively). When PD-L2 status and NLR status were combined, the NLR-low and PD-L2-low were significant factors to predict a favorable disease-free survival (hazard ratio, 4.525 [95% confidence interval, 1.020 to 20.080]; P = 0.047. However, the multivariate analysis failed to show it as an independent factor. Conclusion: These findings suggest that the prognostic impact of PD-L2 expression could be affected by the NLR status.


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