Development of a new assay system for bladder cancer using interactions between cytochromes P450 and serum

Abstract

To overcome bladder cancer, one of the most common cancer and deadly cancers in the world, early diagnosis and treatment interventions are crucial. The development of efficient diagnostic methods is required. Previously, we developed a cytochrome P450 (P450 or CYP) inhibition assay that detected alterations in the quality and quantity of P450 relevant substances in the serum, caused by inflammation and exposure to endogenous or exogenous substances. Since bladder cancer is known to alter the expression levels of P450s in patients, we tested whether the P450 inhibition assay could distinguish between the sera of patients with bladder cancer and healthy individuals. When assays were performed using sera recovered from mice with bladder cancer and control mice, significant differences were observed in the inhibition rates of CYP2A13, CYP2C18 and CYP2E1. Moreover, the results of the assay using human clinical samples revealed that the P450 inhibition assay can detect bladder cancer with an area under the receiver operating characteristic (ROC) curve of 0.867-0.950. These findings demonstrated that the P450 inhibition assay can aid the future development of liquid biopsy-based diagnostic methods for bladder cancer.

Keywords: Biomarker; Bladder cancer; CYP; Cytochrome P450; Diagnosis; Liquid biopsy.