Application of SPRi Biosensors for Determination of 20S Proteasome and UCH-L1 Levels in the Serum and Urine of Transitional Bladder Cancer Patients

Tomasz Guszcz,Ewa Gorodkiewicz,Anna Sankiewicz

doi:10.3390/app11177835

Abstract

The ubiquitin–proteasome system (UPS) participates in the degradation of proteins which play an important role in regulating the cell cycle, apoptosis, and angiogenesis, as well as in the immune system. These processes are important in carcinogenesis. Transitional cell carcinoma (TCC) is one of the predominant types of bladder cancer. The relationship between the ubiquitin–proteasome system and cancer progression has become a topic of increasing interest among researchers. In this work, we propose an application of surface plasmon resonance imaging (SPRi)-based biosensors for the detection of 20S proteasome and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in the blood serum and urine of patients with TCC. The aim of the study was to determine 20S proteasome and UCH-L1 concentrations and to correlate the results with clinicopathological parameters. The group of subjects consisted of 82 patients with confirmed TCC, in addition to a control group of 27 healthy volunteers. It was found that 20S proteasome and UCH-L1 concentrations were significantly elevated in both the serum and urine of TCC patients, compared with the healthy subjects. There was a correlation between 20S proteasome concentrations in serum and urine, as well as between serum proteasome and UCH-L1 concentration. The SPRi biosensor sensitive to 20S proteasome using PSI inhibitor as the receptor, and the SPRi biosensor sensitive to the UCH-L1 protein using the protein-specific antibody as the receptor is suitable for the determination of 20S proteasome and UCH-L1 in body fluids and can serve as useful tools in the investigation of cancer biomarkers.

Highlights

ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), whichwhich belongs to theto family of deubiquitinatproteasome system, the protein
The measurements presented in the paper are the first available data tinating enzymes (DUBs)
The measurements presented in the paper are the first available on concentrations of 20S proteasome and UCH-L1 protein, and their mutual correlation in data on concentrations of 20S proteasome and UCH-L1 protein, and their mutual correlathe serum and urine of bladder cancer patients

Summary

Introduction

Urinary bladder cancer (BCa) is the 10th most common cancer in the world, with an estimated 549,393 diagnosed cases and 200,000 deaths annually. It is the 6th most common malignancy in males and the 17th in females, with age-standardised risks of 9.6% and 2.4%, respectively [1]. This disease can present as non-muscle-invasive bladder cancer (NMIBC), muscleinvasive bladder cancer (MIBC), or the metastatic form of the disease. Tobacco smoking is the most important risk factor for BCa: it is responsible for approximately half of BCa cases and is associated with poor oncological outcomes for both NMIBC and MIBC [2]

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