Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives

Abstract

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.

Role of hypoxia inducible factor-1 in cancer stem cells (Review)

“…Epigenetic modifications are reversible, heritable changes in gene function that do not alter the DNA sequence (26,27). HIF-1α can be used as a key regulator of genomic methylation in hepatocellular carcinoma cells (28).…”

Screening for ovarian cancer: is there still hope?

“…Liquid biopsies are derived from serum, plasma, or other body fluids and may provide noninvasive biomarkers. Their potential to improve early diagnosis is theoretically present but transition to clinic still far [16][17][18].…”

<p>LncRNA GAS8-AS1 Inhibits Ovarian Cancer Progression Through Activating Beclin1-Mediated Autophagy</p>

“…1 Early detection and diagnosis of OC is complicated due to the concealment of the ovarian anatomical position and the lack of clinical manifestations and specific indicators of early OC. 2 Patients are usually in the advanced stage when they are firstly detected, some of them even have peritoneal metastasis or distant metastasis. 3 The recurrence rate of OC and the incidence of poor prognosis are relatively high.…”