Development of DNA methylation biomarker for endometrial cancer detection

Endometrial cancer (EC) is a common gynecological cancer. Endometrial cancer (EC) is a common gynecological cancer. The detection of endometrial cancers are >80% curable in early stage, but dramatic decreasing <30% of cures in late stage. There 1757 new cases occurred and increased 30% of incidence on 2012 in Taiwan. In addition, the incidents of EC are growing up annually in worldwide and Taiwan. However, no feasible screening method for detecting endometrial cancer. There is an urgent need of biomarkers for detecting endometrial cancer patients. The development of effective methods of detection of EC is also needed. Epigenetic alterations have been shown to occur in many types of cancer. Decades of researches have demonstrated the potential of DNA methylation as a marker for early diagnosis of cancer. The genome-side methylation studies could leads to discover novel genes for detection. We analyzed two methylomics data of endometrial cancers for discovery of novel methylation biomarker using various bioinformatics. One set of methylomics data containing 298 samples, and the other containing 89 samples. The candidate genes consistently expressed hypermethylation in two data sets to be conducting further validation by pyrosequencing and quantitative methylation-specific PCR.. The cervical scrapings combining genetic mutation testing is proved a potential biospecimen used to endometrial cancer detection. Testing the methylation of candidate genes will be done using tumor tissues and cervical scraping to verify the clinical potential. We identified four genes to be the EC-detecting panel. Out preliminary data show our EC-detecting panel with excellent sensitivity. However, the methylation level of non-EC samples shows the noise by uteri myoma in cervical scrapings. To improve the sensitivity of EC-detecting panel, we anticipate discovering the myoma specific methylated genes. We aim to determine an EC-detecting panel with >95% sensitivity and 95% specificity for applying the future multiple centre clinical study.