Expression of CYB5D2 is associated with epithelial-mesenchymal transition and survival rates in patients with cervical cancer

BACKGROUND: CYB5D2 is a member of the membrane-associated progesterone receptors (MAPRs) family and plays essential roles in regulating nerve development. CYB5D2 is associated with tumor suppression in breast cancer. Despite the potential implication of CYB5D2 in cancer progression, its level and clinical significance in cervical cancer tissues has not been investigated yet. Via this study, we aimed to investigate the possible role played by CYB5D2 in epithelial–mesenchymal transition (EMT) in cervical cancer and correlate its level with clinical outcomes. METHODS: The expressions of CYB5D2 and the EMT marker E-cadherin in different groups of cervical samples were compared using immunofluorescence. Furthermore, co-localization of CYB5D2 and E-cadherin was analyzed in different cervical tissue samples via confocal laser scanning microscopy. The relationship between CYB5D2/E-cadherin and the progression and clinicopathological features of cervical cancer were analyzed, and the prognostic value of CYB5D2 mRNA expression was evaluated in various tumors using the Kaplan-Meier plotter database. RESULTS: CYB5D2 and E-cadherin were downregulated in cervical cancer (P<0.05). Co-localization of CYB5D2 and E-cadherin in cell cytoplasm in cervical cancer was apparent. The clinical and pathological information of patients with cervical cancer were analyzed, which revealed a statistically significant relationship between low CYB5D2 expression and the tumor FIGO stage (P<0.05). CYB5D2 expression was not correlated with tumors in terms of depth of myometrial invasion, patient age, histological type, and tumor grade (P>0.05). Higher expression levels of CYB5D2 mRNA were predicted to be associated with a better relapse-free survival (RFS) in patients with cervical cancer. E-cadherin expression was associated with invasive tumors, tumor grade, and FIGO stage (P<0.05) but not with patient age and histological type (P>0.05). There was a positive correlation between CYB5D2 and E-cadherin expression in cervical cancer (P<0.01). CONCLUSIONS: These results suggest that CYB5D2 acts as a tumor suppressor in cervical cancer, inhibiting EMT by hindering E-cadherin expression.