J Gynecol Oncol.  2018 Jan;29(1):e17. 10.3802/jgo.2018.29.e17.

The feasibility of detecting endometrial and ovarian cancer using DNA methylation biomarkers in cervical scrapings

Affiliations
  • 1Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • 2Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan. hclai30656@gmail.com, hclai@s.tmu.edu.tw
  • 3Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 4Division of Research and Analysis, Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan.

Abstract


OBJECTIVE
We hypothesized that DNA methylation of development-related genes may occur in endometrial cancer (EC)/ovarian cancer (OC) and may be detected in cervical scrapings.
METHODS
We tested methylation status by quantitative methylation-specific polymerase chain reaction for 14 genes in DNA pools of endometrial and OC tissues. Tissues of EC/normal endometrium, OC/normal ovary, were verified in training set using cervical scrapings of 10 EC/10 OC patients and 10 controls, and further validated in the testing set using independent cervical scrapings in 30 EC/30 OC patients and 30 controls. We generated cutoff values of methylation index (M-index) from cervical scrapings to distinguish between cancer patients and control. Sensitivity/specificity of DNA methylation biomarkers in detecting EC and OC was calculated.
RESULTS
Of 14 genes, 4 (PTGDR, HS3ST2, POU4F3, MAGI2) showed hypermethylation in EC and OC tissues, and were verified in training set. POU4F3 and MAGI2 exhibited hypermethylation in training set were validated in independent cases. The mean M-index of POU4F3 is 78.28 in EC and 20.36 in OC, which are higher than that in controls (6.59; p<0.001 and p=0.100, respectively), and that of MAGI2 is 246.0 in EC and 12.2 in OC, which is significantly higher that than in controls (2.85; p<0.001 and p=0.480, respectively). Sensitivity and specificity of POU4F3/MAGI2 were 83%-90% and 69%-75% for detection of EC, and 61% and 62%-69% for the detection of OC.
CONCLUSION
The findings demonstrate the potential of EC/OC detection through testing for DNA methylation in cervical scrapings.

Keyword

Endometrial Neoplasms; Ovarian Neoplasms; DNA Methylation

MeSH Terms

Biomarkers*
DNA Methylation*
DNA*
Endometrial Neoplasms
Endometrium
Female
Humans
Methylation
Ovarian Neoplasms*
Ovary
Polymerase Chain Reaction
Sensitivity and Specificity
Biomarkers
DNA
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