Cytochrome 4Z1 Expression is Associated with Unfavorable Survival in Triple-Negative Breast Cancers

Abstract

Triple-negative breast cancer (TNBC) is characterized by high mortality rate, and its clinical management is difficult and complex. Therefore, there is a need for extensive efforts aimed at accelerating the discovery of novel therapies for TNBC. CYP4Z1 has been implicated in the development of breast cancer. The current study aimed at characterizing the expression of CYP4Z1 on TNBC. Materials and Methods: Using immunohistochemistry, CYP4Z1 expression was evaluated on 122 TNBC samples, four samples of breast cancers expressing ER, PR, and HER-2, and four samples of normal breast tissues. The association between the enzyme and various histopathological features and survival of patients were determined. Results: CYP4Z1 was strongly expressed in 83.3% of various histopathological subtypes of TNBC, when compared to negative expression in normal breast tissues. Interestingly, there were marked variations in CYP4Z1 expression with respect to histopathology subtype, histological grade, histological stage and tumor diameter. There was a high incidence of CYP4Z1 expression in patients with advanced grades, late stages and larger tumor sizes. Importantly, CYP4Z1 expression was correlated with the survival of TNBC patients, but it was an independent determinant of the poor prognosis of TNBC (p< 0.05). Conclusion: CYP4ZI may be a potential biomarker or target for evolving new CYP4Z1targeted treatments.

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

“…This tendency of CYP4Z1 expression was also observed in lymph node metastasis of breast and cervical cancer patients. 13 , 15 , 16 Our findings are suggestive of the function of CYP4Z1 in colon cancer progression and metastasis.…”

“…CYP4Z1 expression has been reported to be associated with aggressive features in many cancers and is linked with poor survival, particularly in ovarian, prostate, cervical and triple negative breast cancers. 11 , 12 , 15 , 16 In this study, CYP4Z1 expression was associated with low survival rate of colon cancer patients and connoted poor prognosis, which is a novel finding. Moreover, there was a significant association between CYP4Z1 expression and tumour histological grade, the status of lymph node metastasis, and histological stage of colon cancers.…”

“…Several reports demonstrated the expression of CYP4Z1 in a wide variety of primary tumours such as breast, ovary, prostate, bladder and cervix and a lack of expression in normal tissues. 6 , 10–13 , 15 , 16 , 18 , 28 However, there is no information on the presence of CYP4Z1 in metastatic disease. Several studies reported a lack of CYP4Z1 expression in metastatic colon cancers.…”

“… 6 , 7 , 11–15 This overexpression was correlated with an increasing grade of tumour and poor patient outcomes. 11 , 12 , 15 , 16 Moreover, CYP4Z1 was aberrantly expressed at the cell membrane of breast cancer cells and promoted the production of anti-CYP4Z1autoantibodies in the patients’ sera of breast cancer, as opposed to none of the healthy controls. 17 This expression has promoted tumour growth, angiogenesis and the spread of tumour cells.…”

Cytochrome P450 1B1 Overexpression in Cervical Cancers: Cross-sectional Study

“…Several metabolic enzymes, particularly members of the cytochrome P450 (CYP) superfamily, are being investigated for their potential role in tumor malignancy [6][7][8]. Of recent interest is a novel member of the CYP1 gene family, CYP1B1, which is an extrahepatic enzyme that is engaged in the metabolism of several endogenous and xenobiotic compounds [9].…”