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

Hyun Jung Kim, Chan Young Kim, Jinghui Jin, Moon Kyoung Bae, Yun Hee Kim, Woong Ju, Yun Hwan Kim, Seung Cheol Kim

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: 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. Methods: 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. Results: 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%. Conclusion: 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.

Original languageEnglish
Pages (from-to)15-21
Number of pages7
JournalDiagnostic Cytopathology
Volume46
Issue number1
DOIs
StatePublished - Jan 2018

Keywords

  • cervical cancer
  • circulating cell-free DNA
  • diagnostic biomarker
  • DNA methylation
  • single-minded homolog 1(SIM1)

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