Identification of candidate epigenetic biomarkers for ovarian cancer detection

Yi Wen Huang, Rachel A. Jansen, Enrica Fabbri, Dustin Potter, Sandya Liyanarachchi, Michael W Y Chan, Joseph C. Liu, Anne P G Crijns, Robert Brown, Kenneth Nephew, Ate G J Van der Zee, David E. Cohn, Pearlly S. Yan, Tim H M Huang, Huey Jen L Lin

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Ovarian cancer ranks the most lethal among gynecologic neoplasms in women. To develop potential biomarkers for diagnosis, we have identified five novel genes (CYP39A1, GTF2A1, FOXD4L4, EBP, and HAAO) that are hypermethylated in ovarian tumors, compared with the non-malignant normal ovarian surface epithelia, using the quantitative methylation-specific polymerase chain reactions. Interestingly enough, multivariate Cox regression analysis has identified hypermethylation of CYP39A1 correlated with an increase rate of relapsing (P=0.032, hazard ratio >1). Concordant hypermethylation in at least three loci was observed in 50 out of 55 (91%) of ovarian tumors examined. The test sensitivity and specificity were assessed to be 96 and 67% for CYP39A1; 95 and 88% for GTF2A1; 93 and 67% for FOXD4L4; 81 and 67% for EBP; 89 and 82% for HAAO, respectively. Our data have identified, for the first time, GTF2A1 alone, or GTF2A1 plus HAAO are excellent candidate biomarkers for detecting this disease. Moreover, the known functions of these gene products further implicate dysregulated transcriptional control, cholesterol metabolism, or synthesis of quinolinic acids, may play important roles in attributing to ovarian neoplasm. Molecular therapies, by reversing the aberrant epigenomes using inhibitory agents or by abrogating the upstream signaling pathways that convey the epigenomic perturbations, may be developed into promising treatment regimens.

Original languageEnglish
Pages (from-to)853-861
Number of pages9
JournalOncology Reports
Volume22
Issue number4
DOIs
StatePublished - 2009

Fingerprint

Quinolinic Acids
Epigenomics
Ovarian Neoplasms
Female Genital Neoplasms
Biomarkers
Methylation
Genes
Neoplasms
Epithelium
Cholesterol
Regression Analysis
Sensitivity and Specificity
Polymerase Chain Reaction
Therapeutics

Keywords

  • Biomarkers
  • DNA methylation
  • Epigenetics
  • Ovarian cancer
  • Quantitative methylation-specific polymerase chain reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Huang, Y. W., Jansen, R. A., Fabbri, E., Potter, D., Liyanarachchi, S., Chan, M. W. Y., ... Lin, H. J. L. (2009). Identification of candidate epigenetic biomarkers for ovarian cancer detection. Oncology Reports, 22(4), 853-861. https://doi.org/10.3892/or_00000509

Identification of candidate epigenetic biomarkers for ovarian cancer detection. / Huang, Yi Wen; Jansen, Rachel A.; Fabbri, Enrica; Potter, Dustin; Liyanarachchi, Sandya; Chan, Michael W Y; Liu, Joseph C.; Crijns, Anne P G; Brown, Robert; Nephew, Kenneth; Van der Zee, Ate G J; Cohn, David E.; Yan, Pearlly S.; Huang, Tim H M; Lin, Huey Jen L.

In: Oncology Reports, Vol. 22, No. 4, 2009, p. 853-861.

Research output: Contribution to journalArticle

Huang, YW, Jansen, RA, Fabbri, E, Potter, D, Liyanarachchi, S, Chan, MWY, Liu, JC, Crijns, APG, Brown, R, Nephew, K, Van der Zee, AGJ, Cohn, DE, Yan, PS, Huang, THM & Lin, HJL 2009, 'Identification of candidate epigenetic biomarkers for ovarian cancer detection', Oncology Reports, vol. 22, no. 4, pp. 853-861. https://doi.org/10.3892/or_00000509
Huang YW, Jansen RA, Fabbri E, Potter D, Liyanarachchi S, Chan MWY et al. Identification of candidate epigenetic biomarkers for ovarian cancer detection. Oncology Reports. 2009;22(4):853-861. https://doi.org/10.3892/or_00000509
Huang, Yi Wen ; Jansen, Rachel A. ; Fabbri, Enrica ; Potter, Dustin ; Liyanarachchi, Sandya ; Chan, Michael W Y ; Liu, Joseph C. ; Crijns, Anne P G ; Brown, Robert ; Nephew, Kenneth ; Van der Zee, Ate G J ; Cohn, David E. ; Yan, Pearlly S. ; Huang, Tim H M ; Lin, Huey Jen L. / Identification of candidate epigenetic biomarkers for ovarian cancer detection. In: Oncology Reports. 2009 ; Vol. 22, No. 4. pp. 853-861.
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