Blood-based DNA methylation profiling for the detection of ovarian cancer.

Objectives: Ovarian cancer is a fatal gynecological cancer due to the lack of effective screening strategies at early stage. This study explored the utility of DNA methylation profiling of blood samples for the detection of ovarian cancer.

Methods: Targeted bisulfite sequencing was performed on tissue (n = 152) and blood samples (n = 373) obtained from healthy women, women with benign ovarian tumors, or malignant epithelial ovarian tumors. Based on the tissue-derived differentially-methylated regions, a supervised machine learning algorithm was implemented and cross-validated using the blood-derived DNA methylation profiles of the training cohort (n = 178) to predict and classify each blood sample as malignant or non-malignant. The model was further evaluated using an independent test cohort (n = 184).

Results: Comparison of the DNA methylation profiles of normal/benign and malignant tumor samples identified 1272 differentially-methylated regions, with 49.4% hypermethylated regions and 50.6% hypomethylated regions. Five-fold cross-validation of the model using the training dataset yielded an area under the curve of 0.94. Using the test dataset, the model accurately predicted non-malignancy in 96.2% of healthy women (n = 53) and 93.5% of women with benign tumors (n = 46). For patients with malignant tumors, the model accurately predicted malignancy in 44.4% of stage I-II (n = 9), 86.4% of stage III (n = 59), 100.0% of stage IV tumors (n = 6), and 81.8% of tumors with unknown stage (n = 11). Overall, the model yielded a predictive accuracy of 89.5%.

Conclusions: Our study demonstrates the potential clinical application of blood-based DNA methylation profiling for the detection of ovarian cancer.