Screening of cytochrome 4Z1 expression in human non-neoplastic, pre-neoplastic and neoplastic tissues

29 Sep 2020
Yousef M Al-saraireh, Nafea S Alboaisa, Hamzeh Mohammad Alrawashdeh, Omar Hamdan, Sameeh Al-Sarayreh, Jehad M Al-Shuneigat, Mohammad N Nofal

Background: Cytochromes P450 (CYPs) constitute an enzyme family involved in the oxidative metabolism of a wide variety of endogenous and exogenous compounds, including anti-cancer drugs and carcinogens. Unlike other human CYPs, CYP4Z1 is highly expressed in human breast carcinoma and is associated with poor prognosis. As a result, CYP4Z1 was hypothesised to be a potential biomarker or drug target for the discovery and development of promising anti-cancer therapies.

Materials and methods: CYP4Z1 expression was immunohistochemically studied in a set of 100 different human tissues, including normal, benign, malignant and metastatic tissues, which originated from 27 anatomical sites. As a tumour model for CYP4Z1 expression, a panel of different breast cancers was evaluated for CYP4Z1 expression and its relation to histopathological features and prognostic immunohistochemical markers.

Results: The immunohistochemical results revealed that CYP4Z1 was expressed in only one (4.3%) of the normal tissues from the mammary glands, while the expression of the enzyme was positive in 1 (11%), 12 (19%) and 2 (40%) of the benign, malignant and metastatic tissues, respectively. Interestingly, several tumour entities showed prominent expressions of CYP4Z1, including carcinomas of adrenal cortex, squamous cells of oesophagus, lung and cervix, as well as seminoma, astrocytoma, melanoma and lastly endometrial adenocarcinoma. In breast cancers, CYP4Z1 was expressed in 82% of the cases. Its expression was significantly associated with the pathology of tumour, histological grade and status of lymph node metastasis. Importantly, it was also significantly associated with the expressions of Her2, P53 and Ki-67.

Conclusion: These findings greatly support future plans for the use of CYP4Z1 as a biomarker or target for anti-cancer drugs. However, large-scale validation studies are needed to better delineate the potential use of CYP4Z1 for therapeutic purposes.

Article metrics: 700 views

Related Articles

Gunjesh Kumar Singh, Hollis DSouza, Nandini Menon, Sujay Srinivas, Dilip Harindran Vallathol, Mounika Boppana, Annu Rajpurohit, Abhishek Mahajan, Amit Janu, Abhishek Chatterjee, Rahul Krishnatry, Tejpal Gupta, Rakesh Jalali, Vijay M Patil
Paul Summers, Giulia Saia, Alberto Colombo, Paola Pricolo, Fabio Zugni, Sarah Alessi, Giulia Marvaso, Barbara Alicja Jereczek-Fossa, Massimo Bellomi, Giuseppe Petralia
Santam Chakraborty, Idranil Mallick, Hung N Luu, Tapesh Bhattacharyya, Moses Arunsingh, Rimpa Basu Achari, Sanjoy Chatterjee
Gabriela Candás, Alejandra García, María Delfina Ocampo, Ernesto Korbenfeld, H Daniel Vuoto, Juan Isetta, Lucas Cogorno, Agustina González Zimmermann, Marca Sigal, Santiago Acevedo, Julia Berwart, Martín Naveira, Agustina Bemi, Juan Luis Uriburu
Maria Gosein, Laura Mohammed, Adrian Chan, Alexander Sinanan, Renee Banfield, Paramanand Maharaj, Dylan Narinesingh