Journal
JOURNAL OF GYNECOLOGIC ONCOLOGY
Volume 29, Issue 1, Pages -Publisher
KOREAN SOC GYNECOLOGY ONCOLOGY & COLPOSCOPY
DOI: 10.3802/jgo.2018.29.e17
Keywords
Endometrial Neoplasms; Ovarian Neoplasms; DNA Methylation
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Funding
- Tri-Service General Hospital [TSGH-C104-006-006-008-S01, TSGH-C104-006-006-008-S02, TSGH-C105-010]
- Ministry of Science and Technology [NSC 105-2628-B-038-011-MY3, NSC 103-2325-B-195-002]
- Taipei Medical University [104TMU-SHH-07]
- Ministry of Health and Welfare [MOHW105-TDU-PB-212-000007]
- National Health Research Institutes [NHRI-EX106-10406BI]
- Teh-Tzer Study Group for Human Medical Research Foundation
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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.
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