Soluble PD-L1 in Serum and Urine in Urinary Bladder Cancer Patients.

Anders Vikerfors,Tomas Jerlström,Janusz Frey,Jessica Carlsson,Sabina Davidsson

doi:10.3390/cancers13225841

Abstract

Simple SummaryNon-invasive diagnostic and prognostic biomarkers for urinary bladder cancer (BC) are eagerly awaited, since these could improve patient’s quality of life and reduce resources and costs for the health care system. The PD-1/PD-L1 axis is an important immune escape mechanism for tumors, and both high tissue expression and soluble levels of PD-L1 have been shown to be associated with worse prognosis for patients with various tumor. The knowledge about soluble PD-L1 in body fluids such as serum and urine in patients with BC is sparse, and more studies are needed to investigate its role as a biomarker for the disease. In the present study, we show that high serum PD-L1 levels are associated with aggressive disease and development of metastatic disease in BC patients.Soluble PD-L1 (sPD-L1) levels have been identified as a potential biomarker for various cancers, but its diagnostic and prognostic value in urinary bladder cancer (BC) remains to be fully elucidated. In this study, we investigated sPD-L1 levels in serum and urine samples from 132 patients with BC and compared them to 51 patients with hematuria (controls). The levels of sPD-L1 in serum and urine were determined using ELISA. Soluble PD-L1 could be detected in 99.5% of the serum samples and 34.4% of the urine samples. Patients diagnosed with BC had significantly higher urinary levels of sPD-L1, compared to controls, however no difference were found in serum sPD-L1 levels (p = 0.038 and p = 0.61, respectively). Significantly higher serum sPD-L1 levels were found in patients with muscle invasive disease and metastatic disease, compared to patients with non-muscle invasive BC and non-metastatic disease (p < 0.05). There was also a trend for higher urine sPD-L1 levels in patients with metastatic disease, compared to patients with non-metastatic disease (p = 0.05). The results from this study suggest that sPD-L1 in serum, but not in urine, could be a potential prognostic biomarker for patients with BC.

Highlights

Urothelial bladder cancer (BC) is the ninth most common cancer worldwide with an estimation of 549,000 new diagnoses in 2018, and each year 200,000 people die due to the disease [1]
Patients were recruited from the BLAdder cancer Blood and Urine Study (BLABUS), a prospective cohort study consisting of patients with macroscopic hematuria who were referred to the Department of Urology at the University hospital of Örebro for suspicion of bladder cancer
These patients were excluded from further analyses regarding Soluble programmed cell death ligand 1 (PD-L1) (sPD-L1) and its association with clinical parameters, leaving 118 cases left in the analyses

Summary

Introduction

Urothelial bladder cancer (BC) is the ninth most common cancer worldwide with an estimation of 549,000 new diagnoses in 2018, and each year 200,000 people die due to the disease [1]. The majority of BC (~75%) initially present as superficial, non-muscle invasive (NMIBC) tumors that are confined to the urothelium or the lamina propria [2]. These tumors are characterized by a high recurrence rate, and progression to a muscle-invasive bladder cancer (MIBC) occurs in 10–30% among patients with high grade tumors [3]. Patients with a MIBC have a worse prognosis, with a 5-year survival rate of 20–35% compared to 60–80%. Introduction of non-invasive diagnostic and prognostic biomarkers for BC are eagerly awaited since these could reduce the number of unnecessary cystoscopies, 4.0/)

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