Ovarian cancer is one of the deadliest gynecological cancers, partly because early detection is difficult. Traditional blood markers like CA125 and HE4 often miss early-stage disease, and tissue biopsies cannot capture the full complexity of tumors. cfDNA methylation liquid biopsy is emerging as a non-invasive and highly sensitive alternative for diagnosis, prognosis, and monitoring treatment.
DNA methylation is a chemical change where methyl groups attach to specific DNA regions, often silencing tumor-suppressor genes early in cancer development. Detecting these changes in circulating cell-free DNA (cfDNA) allows earlier detection than imaging, helps identify the tumor’s tissue of origin, and provides real-time monitoring because cfDNA has a very short half-life.
Researchers have identified specific genes, such as RASSF1A and BRCA1, whose methylation in blood signals ovarian cancer. Panels combining multiple genes (e.g., HOXA9 + HIC1 or an 18-gene model) have reached sensitivities of 88–95%, outperforming CA125 tests. Liquid biopsies can also detect minimal residual disease months before imaging, predict recurrence, and track treatment resistance. For example, methylation of hMLH1 indicates platinum chemotherapy resistance, while BRCA1 or HOXA9 changes can inform survival predictions. This approach allows earlier intervention, better monitoring of therapy effectiveness, and personalized treatment strategies.