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. 2021 Nov 12:14:5249-5260.
doi: 10.2147/OTT.S332037. eCollection 2021.

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

Yousef M Al-Saraireh  1 , Fatemah O F O Alshammari  2 , Ahmed M M Youssef  3 , Sameeh Al-Sarayreh  4 , Ghadeer H Almuhaisen  5 , Nedal Alnawaiseh  6 , Jehad M Al-Shuneigat  4 , Hamzeh M Alrawashdeh  7
Affiliations

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

Yousef M Al-Saraireh et al. Onco Targets Ther. .

Abstract

Purpose: 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 4Z1; cytochrome P450; immunohistochemistry.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Different scores and immunostaining pattern of CYP4Z1 expression in colon cancers. CYP4Z1 immunoreactivity was predominantly localized to the membrane or cytoplasm of cells without any considerable staining in nuclei. (A) Score “negative” showing no expression in the tissue at all. (B) Score “low” showing expression less than 33% of cells, (C) score “moderate” showing expression in 34–66% of the cells, (D) score “strong” showing expression in more than 67% of the cells. Magnification (X400).
Figure 2
Figure 2
CYP4Z1 expression in different types of colon tissues. Tumours were classified on the basis of histological type. (A) Normal colon tissue, (B) colon tubular adenoma, (C) colon adenocarcinoma, (D) metastatic adenocarcinoma from colon, (E) Metastatic mucinous adenocarcinoma and (F) metastatic signet-ring cell carcinoma. Magnification (X400).
Figure 3
Figure 3
CYP4Z1 expression in different types of experimental controls. (A) No CYP4Z1 expression in colon cancer tissue incubated with normal goat serum instead of CYP4Z1primary antibody (negative control), (B) high CYP4Z1 expression was displayed in colon cancer tissue incubated with CYP4Z1 primary antibody, (C) weak to no expression of CYP4Z1 was exhibited in colon cancer tissue incubated with mixture of primary antibody and blocking peptide, (D) high CYP4Z1 expression was displayed in breast cancer tissue incubated with CYP4Z1 primary antibody (positive control) and (E) very weak expression of CYP4Z1 was observed in breast cancer tissue incubated with mixture of primary antibody and blocking peptide. Magnification (x400).
Figure 4
Figure 4
CYP4Z1 expression in normal, benign, primary and metastatic colon samples.
Figure 5
Figure 5
Kaplan–Meier curve showing overall survival of colon cancer patients.
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