5-Hydroxymethylcytosine expression is associated with poor survival in cervical squamous cell carcinoma

Abstract

Objective: Deoxyribonucleic acid methylation is an important epigenetic modification that is frequently altered in cancer. Recent reports showed that the level of 5-hydroxymethylcytosine was altered in various types of cancers. The influence of deoxyribonucleic acid methylation in cervical squamous cell carcinoma is not fully understood. In this study, we investigated 5-hydroxymethylcytosine and ten-eleven translocation expression in cervical squamous cell carcinoma and whether they are associated with poor survival in cervical squamous cell carcinoma.

Methods: We detected the expression of 5-hydroxymethylcytosine, 5-methylcytosine and TET1/2/3 in 140 patients with cervical squamous cell carcinoma and 40 patients with normal cervical tissues by immunohistochemistry. We assessed the prognostic values of 5-hydroxymethylcytosine, 5-methylcytosine and TET2 in the clinical outcome of cervical squamous cell carcinoma.

Results: Expression of 5-hydroxymethylcytosine was significantly decreased in cervical squamous cell carcinoma compared with normal cervix tissues. In contrast, 5-methylcytosine expression was significantly increased in cervical squamous cell carcinoma compared with normal cervix tissues. Moreover, expression of TET2, but not TET1 and TET3, was decreased in cervical squamous cell carcinoma. Our study showed that the decreased level of 5-hydroxymethylcytosine predicts poor prognosis of cervical squamous cell carcinoma patients. The expression of 5-hydroxymethylcytosine was an independent prognostic factor for both disease-free and overall survival of cervical squamous cell carcinoma patients.

Conclusions: In cervical squamous cell carcinoma, less aggressive tumor behavior was correlated with 5-hydroxymethylcytosine and TET2. Our data indicated that 5-hydroxymethylcytosine may become a prognostic marker for cervical squamous cell carcinoma and the decreased expression of TET2 may be an underlying mechanism for decreased 5-hmC in cervical squamous cell carcinoma.

Keywords: 5-hydroxymethylcytosine; cervical squamous cell carcinoma; immunohistochemistry; survival; ten–eleven translocation.