Circulating Cell-Free DNA Methylation Profiles in the Early Detection of Ovarian Cancer: A Scoping Review of the Literature.

Lynda D. Roman,Bodour Salhia,Xiaoyue M. Guo,Heather Miller,Koji Matsuo

doi:10.3390/cancers13040838

Abstract

Simple SummaryThere are limited non-invasive methods for detecting epithelial ovarian cancer despite early detection and treatment dramatically increasing survival. As alterations in serum or plasma cell-free (cf)DNA methylation occur early in cancer development, they are promising biomarkers for ovarian cancer. Our literature review includes 18 studies depicting a wide array of gene targets and techniques. The data suggest a good performance of these cfDNA methylation tests, with accuracies up to 91% in detecting ovarian cancer in serum or plasma.Epithelial ovarian cancer is the most lethal gynecologic malignancy and has few reliable non-invasive tests for early detection or diagnosis. Recent advances in genomic techniques have bolstered the utility of cell-free DNA (cfDNA) evaluation from peripheral blood as a viable cancer biomarker. For multiple reasons, comparing alterations in DNA methylation is particularly advantageous over other molecular assays. We performed a literature review for studies exploring cfDNA methylation in serum and plasma for the early diagnosis of ovarian cancer. The data suggest that serum/plasma cfDNA methylation tests have strong diagnostic accuracies for ovarian cancer (median 85%, range 40–91%). Moreover, there is improved diagnostic performance if multiple genes are used and if the assays are designed to compare detection of ovarian cancer with benign pelvic masses. We further highlight the vast array of possible gene targets and techniques, and a need to include more earlier-stage ovarian cancer samples in test development. Overall, we show the promise of cfDNA methylation analysis in the development of a viable diagnostic biomarker for ovarian cancer.

Highlights

Epithelial ovarian cancer (OC) is the most lethal gynecologic malignancy with a 5-year survival rate under 50%
Better diagnostic performance was appreciated for studies that included benign masses as comparison arms instead of only healthy controls and when multiple genes were evaluated for methylation status instead of a single gene
Despite ample attempts at studying biomarkers and algorithms, efforts have fallen short in identifying a reliable strategy for the detection of ovarian cancer [4]

Summary

Introduction

Epithelial ovarian cancer (OC) is the most lethal gynecologic malignancy with a 5-year survival rate under 50%. The Food and Drug Administration (FDA) has approved various new serum biomarkers and biomarker panels (i.e., human epididymis protein 4, Aspira Labs’ OVA1 and Overa comprising CA125, apolipoprotein A1, beta-2 microglobulin, transferrin, and pre-albumin) as well as multimodal tests including transvaginal ultrasounds (i.e., the risk of malignancy index or Roche Diagnostics’ risk of ovarian malignancy algorithm) [8]. These approaches have been largely inadequate as they have not yielded a shift in the diagnosis of OC, especially at the earlier stages. They lack the sensitivity and specificity to be considered screening tests [7,9] and are not currently recommended for clinical use by any governing organization

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