“Epigenetic Biomarkers in the management of ovarian cancer: current prospectives”

摘要

Ovarian cancer (OC) causes significant morbidity and mortality as neither detection nor screening of OC is currently feasible at an early stage. Difficulty to promptly diagnose OC in its early stage remains challenging due to non-specific symptoms in the early-stage of the disease, their presentation at an advanced stage and poor survival. Therefore, improved detection methods are urgently needed. In this article, we summarize the potential clinical utility of epigenetic signatures like DNA methylation, histone modifications, and microRNA dysregulation, which play important role in ovarian carcinogenesis and discuss its application in development of diagnostic, prognostic and predictive biomarkers. Molecular characterization of epigenetic modification (methylation) in circulating cell free tumor DNA in body fluids offers novel, non invasive approach for identification of potential promising cancer biomarkers, which can be performed at multiple time points and probably better reflects the prevailing molecular profile of cancer. Current status of epigenetic research in diagnosis of early OC and its management are discussed here with main focus on potential diagnostic biomarkers in tissue and body fluids. Rapid and point of care diagnostic applications of DNA methylation in liquid biopsy has been precluded as a result of cumbersome sample preparation with complicated conventional methods of isolation. New technologies which allow rapid identification of methylation signatures directly from blood will facilitate sample-to answer solutions thereby enabling next-generation point of care molecular diagnostics. To date, not a single epigenetic biomarker which could accurately detect ovarian cancer at an early stage in either tissue or body fluid has been reported. Taken together, the methodological drawbacks, heterogeneity associated with ovarian cancer and non validation of the clinical utility of reported potential biomarkers in larger ovarian cancer populations has impeded the transition of epigenetic biomarkers from lab to clinical settings. Until addressed, clinical implementation as a diagnostic measure is a far way to go.