Expression of CYP4X1 in colorectal carcinoma is associated with metastasis and poor prognosis

Abstract

Background Colorectal cancer (CRC) is the third most common cancer and has the second highest mortality rate. The recurrence rate of colorectal cancer is 30–50%, and the survival rate of patients with recurrence and metastasis is very low. Prognostic biomarkers of colorectal cancer can be guidelines for the therapeutic management of the cancer patients. The cytochrome P450 (CYP) family is upregulated in various cancers and contributes to cancer cell proliferation, signaling and drug metabolism. In addition, the Cytochrome P450 family is related to various xenobiotics and endogenous compounds. Nevertheless, the role of CYP4X1 in regulating the progression and growth of colorectal cancer remains unclear. Methods To investigate the relationship between CYP4X1 expression and colorectal cancer, CYP4X1 expression was inhibited in colorectal cancer cells using siRNA and confirmed at mRNA and protein levels. WST-1, Transwell and colony formation assays were performed using CYP4X1 downregulated cells. We performed immunohistochemistry for the CYP4X1 expression of 243 colorectal cancer tissues and investigated the expression with the patient’s clinical parameters. Results In colorectal cancer, downregulated CYP4X1 suppressed proliferation, migration, invasion, and colony formation. CYP4X1 overexpression was found to be related to TNM stage, degree of tumor differentiation, invasion of the primary tumor, clinical stages, and lymph node metastasis. In addition, the high CYP4X1 expression revealed a shorter survival period than those with low CYP4X1 expression by Kaplan-Meier survival analysis. Conclusions Upregulated CYP4X1 may be an independent prognostic marker for CRC, and CYP4X1 may be a therapeutic target for CRC patients. Epoxyeicosatrienoic acid (EET) derived from arachidonic acid has been implicated in carcinogenesis due to its CYP polymorphism. Whether CYP4X1 regulates EET in CRC remains unknown. Therefore, the increased CYP4X1 in EET requires further studies on the correlation between EGFR phosphorylation and PI3K/AKT and MAPK signaling.