Profiling of CYP4Z1 and CYP1B1 expression in bladder cancers

Yousef M Al-Saraireh,Nedal Alnawaiseh,Jehad M Al Shuneigat,Ahmed M M Youssef,Hamzeh M Alrawashdeh,Sameeh Al-Sarayreh,Ghadeer H Almuhaisen,Fatemah O F O Alshammari

doi:10.1038/s41598-021-85188-4

Yousef M Al-Saraireh, Nedal Alnawaiseh + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-85188-4

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Abstract

Bladder cancer is the tenth most common cancer worldwide, where its burden remains a challenge and needs new novel therapies. Several reports indicate expression of CYP4Z1 and CYP1B1 in many tumours. Their expressions are associated with a poor prognosis, and therefore proposed as promising biomarkers or targets for anticancer therapy. By using immunohistochemistry, expression of CYP4Z1 and CYP1B1 was evaluated in a panel of different types of bladder cancer, and the enzymes’ relation to histopathological features were assessed. Results showed an increased expression of CYP4Z1 (54.3%) and CYP1B1 (76.9%) in the majority of bladder cancers compared to weak or lack of expression of both enzymes in normal tissues. CYP4Z1expression was significantly associated with tumour grade and stage where the expression was markedly increased in a high grade and advanced stage of the disease (p < 0.05). Additionally, CYP1B1 expression was also associated with TNM staging (p < 0.05) and its expression was increased in patients with lymph node metastasis. The expression profiles of CYP4Z1 and CYP1B1 suggest that both enzymes have the potential to be biomarkers or targets for novel anticancer therapy for bladder cancer. Nevertheless, further studies are needed to better delineate whether these enzymes are druggable targets.

Highlights

Bladder cancer is the tenth most common cancer worldwide, where its burden remains a challenge and needs new novel therapies
Considering the fact that, and until the date of this paper, there are no prior studies assessing the expression of CYP4Z1 and CYP1B1 in bladder cancers, this study aims to examine the aberrant expression of CYP4Z1 and CYP1B1 in different subtypes of bladder cancer and correlate their expressions with baseline demographic and clinicopathologic features
The most common bladder cancer subtype among the patients enrolled in this study was urothelial carcinoma (160 cases, 76.9%)

Summary

Introduction

Bladder cancer is the tenth most common cancer worldwide, where its burden remains a challenge and needs new novel therapies. Several reports indicate expression of CYP4Z1 and CYP1B1 in many tumours Their expressions are associated with a poor prognosis, and proposed as promising biomarkers or targets for anticancer therapy. The expression profiles of CYP4Z1 and CYP1B1 suggest that both enzymes have the potential to be biomarkers or targets for novel anticancer therapy for bladder cancer. Many metabolic enzymes are currently under examination for their potential roles in bladder cancer susceptibility Of these are members of the cytochrome P450 (CYP) family, CYP4Z1 and CYP1B1. CYP4Z1 expression enhanced tumour growth, angiogenesis and the spread of tumour cells in both in vitro and in vivo models These effects were due to decrease in the levels of myristic and lauric acids and the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) by C YP4Z113. The study further proposed that CYP4Z1 may promote the tumourgenesis by a mechanism other than the direct production of 20-HETE15

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