Identification of candidate epigenetic biomarkers for ovarian cancer detection. Oncol Rep 2009 Oct;22(4):853-61
Date
09/03/2009Pubmed ID
19724865Pubmed Central ID
PMC2829240Scopus ID
2-s2.0-70350398901 (requires institutional sign-in at Scopus site) 43 CitationsAbstract
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.
Author List
Huang YW, Jansen RA, Fabbri E, Potter D, Liyanarachchi S, Chan MW, Liu JC, Crijns AP, Brown R, Nephew KP, van der Zee AG, Cohn DE, Yan PS, Huang TH, Lin HJMESH terms used to index this publication - Major topics in bold
3-Hydroxyanthranilate 3,4-DioxygenaseBiomarkers, Tumor
CpG Islands
DNA Methylation
Epigenesis, Genetic
Female
Forkhead Transcription Factors
Humans
Middle Aged
Neoplasm Staging
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms
Reverse Transcriptase Polymerase Chain Reaction
Sensitivity and Specificity
Steroid Hydroxylases
Steroid Isomerases
Transcription Factors, TFII
