Promoter Methylation of Ezrin and its Impact on the Incidence and Prognosis of Cervical Cancer

Abstract

Background/aims: Aberrant localization and over-expression of Ezrin have been reported to be implicated in cervical cancer (CC). Aberrant promoter methylation of some gene families may serve as potential diagnostic biomarkers for CC. In this study, we explored the correlation of promoter methylation of the Ezrin gene with the incidence and prognosis of CC.

Methods: Cervical tissues from a total of 483 patients with CC were collected from the China-Japan Union Hospital of Jilin University. Samples were assigned into four groups accordingly to pathological diagnosis, namely the control group, the cervical intraepithelial neoplasia (CIN) I group, the CIN II-III group and the CC group. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expression of Ezrin. Methylation-specific polymerase chain reaction (MSP) was used to detect the promoter methylation of the Ezrin gene. The Kaplan-Meier product-limit method and the log-rank analysis were used for survival analysis, the Cox regression analysis for the prognostic factors for CC, and the logistic regression analysis for the risk factors for the occurrence of CC.

Results: The methylation rate of the Ezrin gene was correspondingly increased from the control, the CIN I, the CIN II-III to the CC groups. Over-expressed mRNA of Ezrin was determined in CC tissues. The mRNA expression of Ezrin was correlated with tumor size, lymphatic metastasis, pathological grade and clinical stage (FIGO). The risk factors for the occurrence of CC were the number of abortions and the promoter methylation of the Ezrin gene. Poor prognosis of CC correlated to lymphatic metastasis, higher pathological grade, higher FIGO stage and positive Ezrin promoter methylation.

Conclusion: These findings indicate that promoter methylation of the Ezrin gene may play a crucial role in carcinogenesis, progression and prognosis of CC.

Keywords: Cervical cancer; Ezrin gene; Incidence; Methylation; Prognosis.