Cytochrome 4Z1 Expression is Associated with Poor Prognosis in Colon Cancer Patients

Yousef M Al-saraireh,1 Fatemah OFO Alshammari,2 Ahmed MM youssef,3 Sameeh Al-Sarayreh,4 Ghadeer H Almuhaisen,5 Nedal Alnawaiseh,6 Jehad M Al-Shuneigat,4 Hamzeh M Alrawashdeh7 1Department of Pharmacology, Faculty of Medicine, Mutah University, Al-Karak, Jordan; 2Department of Medical Laboratory Technology, Faculty of Health Sciences, The Public Authority for Applied Education and Training, Shuwaikh, Kuwait; 3Department of Pharmacology, Faculty of Pharmacy, Mutah University, Al-Karak, Jordan; 4Department of Biochemistry and Molecular Biology, Faculty of Medicine, Mutah University, Al-Karak, Jordan; 5Department of Microbiology and Pathology, Faculty of Medicine, Mutah University, Al- Karak, Jordan; 6Department of Public Health, Faculty of Medicine, Mutah University, Al-Karak, Jordan; 7Department of Ophthalmology, Sharif Eye Centers, Irbid, JordanCorrespondence: Yousef M Al-sarairehDepartment of Pharmacology, Faculty of Medicine, Mutah University, PO. Box: 7, Al-Karak, 61710, JordanTel +962799172658Email Yousef.sar@mutah.edu.joPurpose: Colon cancer is a leading cause of mortality worldwide. It has a relatively poor prognosis; therefore, new therapies are needed. One of the tumour-related enzymes that has gained considerable interest is CYP4Z1. This enzyme has been expressed in many tumours and has been hypothesized as a potential biomarker or target for novel anticancer therapies.Patients and Methods: CYP4Z1 overexpression was immunohistochemically examined in a large panel of colon tissue types including normal, benign, primary and metastatic ones, and the enzyme’s relation to histopathological features and patient survival was evaluated.Results: A high CYP4Z1 expression was observed in benign, primary and metastatic colon tissues compared to a weak or lack of expression in normal tissues. Importantly, there was a significant differential in CYP4Z1 expression where it was stronger in metastatic, primary and benign, respectively (p < 0.05). A significantly high rate of CYP4Z1 expression was found in high histological grades and late stages of the disease, where its expression was more evident in patients with metastasis in the lymph nodes (p < 0.05). Interestingly, CYP4Z1 expression was identified an independent prognostic predictor of poor overall survival of colon cancer patients (p = 0.003).Conclusion: CYP4Z1 was distinctly overexpressed in benign, primary and metastatic colon tissues compared to corresponding normal tissues. This differential in CYP4Z1 expression across different types of colon tissues strongly supports CYP4Z1 as potential biomarker and target for novel anticancer therapy development.Keywords: cancer, colon cancer, cytochrome P450, cytochrome 4Z1, immunohistochemistry