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

Cheng Chang Chang, Hui Chen Wang, Yu Ping Liao, Yu Chih Chen, Yu Chun Weng, Mu Hsien Yu, Hung Cheng Lai

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Article numbere17
JournalJournal of Gynecologic Oncology
Volume29
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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DNA Methylation
Endometrial Neoplasms
Ovarian Neoplasms
Biomarkers
Methylation
Genes
Sensitivity and Specificity

Keywords

  • DNA methylation
  • Endometrial neoplasms
  • Ovarian neoplasms

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

Cite this

The feasibility of detecting endometrial and ovarian cancer using DNA methylation biomarkers in cervical scrapings. / Chang, Cheng Chang; Wang, Hui Chen; Liao, Yu Ping; Chen, Yu Chih; Weng, Yu Chun; Yu, Mu Hsien; Lai, Hung Cheng.

In: Journal of Gynecologic Oncology, Vol. 29, No. 1, e17, 01.01.2018.

Research output: Contribution to journalArticle

Chang, Cheng Chang ; Wang, Hui Chen ; Liao, Yu Ping ; Chen, Yu Chih ; Weng, Yu Chun ; Yu, Mu Hsien ; Lai, Hung Cheng. / The feasibility of detecting endometrial and ovarian cancer using DNA methylation biomarkers in cervical scrapings. In: Journal of Gynecologic Oncology. 2018 ; Vol. 29, No. 1.
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title = "The feasibility of detecting endometrial and ovarian cancer using DNA methylation biomarkers in cervical scrapings",
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.",
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AB - 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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