Aberrant single-minded homolog 1 methylation as a potential biomarker for cervical cancer.

Abstract

The aim of this study is to evaluate the possibility of using the methylation status of single-minded homolog 1 (SIM1) as a diagnostic biomarker for cervical cancer. All the patient and normal specimens including the normal cervix (n = 10), cervical cancer tissues (n = 45), blood (n = 45), and cervical brush specimens (n = 110) were retrospectively obtained. Quantitative methylation-specific PCR was performed to detect SIM1 methylation in primary tumors, cervical brush specimens, and plasma circulating cell-free DNA (ccfDNA). SIM1 expression was detected by western blot analysis. We found that SIM1 was highly methylated in the majority of the cervical cancer tissues that we tested, but not in any of the normal tissues. Hypermethylation of SIM1 led to a pronounced reduction in SIM1 expression in cervical cancer tissues compared with normal cervix. SIM1 methylation status on cervical brush specimens also distinguished cervical cancer from normal, cervical intraepithelial neoplasia (CIN) 1 and 2. The degree of SIM1 methylation was significantly associated with the severity of the disease (Ptrend < .0001). We also investigated the possibility of detecting methylated SIM1 in plasma ccfDNA from cervical cancer patients. Methylated SIM1 was detected in 36.6% (15/41) of ccfDNA samples, and concordance rate with the matched cancer tissues was 41.5% (17/41) with sensitivity 38.5% and specificity 100%. This study has shown that SIM1 is frequently hypermethylated in cervical cancer, compared with normal cervix tissue, CIN1 and 2 samples, suggesting that the methylation status of SIM1 could be a potential diagnostic biomarker for cervical cancer.