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Detection of ovarian cancer using plasma cell-free DNA methylomes

Authors
  • Lu, Huaiwu
  • Liu, Yunyun
  • Wang, Jingyu
  • Fu, Shaliu
  • Wang, Lingping
  • Huang, Chunxian
  • Li, Jing
  • Xie, Lingling
  • Wang, Dongyan
  • Li, Dan
  • Zhou, Hui
  • Rao, Qunxian
Type
Published Article
Journal
Clinical Epigenetics
Publisher
Springer-Verlag
Publication Date
Jun 09, 2022
Volume
14
Identifiers
DOI: 10.1186/s13148-022-01285-9
PMID: 35681212
PMCID: PMC9185905
Source
PubMed Central
Keywords
Disciplines
  • Research
License
Unknown

Abstract

Background Ovarian cancer (OC) is a highly lethal gynecologic cancer, and it is hard to diagnose at an early stage. Clinically, there are no ovarian cancer-specific markers for early detection. Here, we demonstrate the use of cell-free DNA (cfDNA) methylomes to detect ovarian cancer, especially the early-stage OC. Experimental design Plasma from 74 epithelial ovarian cancer patients, 86 healthy volunteers, and 20 patients with benign pelvic masses was collected. The cfDNA methylomes of these samples were generated by cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq). The differentially methylated regions (DMRs) were identified by the contrasts between tumor and non-tumor groups, and the discrimination performance was evaluated with the iterative training and testing method. Results The DMRs identified for cfDNA methylomes can well discriminate tumor groups and non-tumor groups (ROC values from 0.86 to 0.98). The late-stage top 300 DMRs are more late-stage-specific and failed to detect early-stage OC. However, the early-stage markers have the potential to discriminate all-stage OCs from non-tumor samples. Conclusions This study demonstrates that cfDNA methylomes generated with cfMeDIP-seq could be used to identify OC-specific biomarkers for OC, especially early OC detection. To detect early-stage OC, the biomarkers should be directly identified from early OC plasma samples rather than mix-stage ones. Further exploration of DMRs from a k larger early-stage OC cohort is warranted. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-022-01285-9.

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