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. 2021 Dec 21;14(1):4.
doi: 10.3390/cancers14010004.

Prognostic Significance of SLFN11 Methylation in Plasma Cell-Free DNA in Advanced High-Grade Serous Ovarian Cancer

Victoria Tserpeli  1 , Dimitra Stergiopoulou  1 , Dora Londra  1 , Lydia Giannopoulou  1 , Paul Buderath  2 , Ioanna Balgkouranidou  3 , Nikolaos Xenidis  3 , Christina Grech  4 , Eva Obermayr  4 , Robert Zeillinger  4 , Kitty Pavlakis  5 , Theodoros Rampias  6 , Stylianos Kakolyris  3 , Sabine Kasimir-Bauer  2 , Evi S Lianidou  1
Affiliations

Prognostic Significance of SLFN11 Methylation in Plasma Cell-Free DNA in Advanced High-Grade Serous Ovarian Cancer

Victoria Tserpeli et al. Cancers (Basel). .

Abstract

Background: Epigenetic alterations in ctDNA are highly promising as a source of novel potential liquid biopsy biomarkers and comprise a very promising liquid biopsy approach in ovarian cancer, for early diagnosis, prognosis and response to treatment.

Methods: In the present study, we examined the methylation status of six gene promoters (BRCA1, CST6, MGMT, RASSF10, SLFN11 and USP44) in high-grade serous ovarian cancer (HGSOC). We evaluated the prognostic significance of DNA methylation of these six gene promoters in primary tumors (FFPEs) and plasma cfDNA samples from patients with early, advanced and metastatic HGSOC.

Results: We report for the first time that the DNA methylation of SLFN11 in plasma cfDNA was significantly correlated with worse PFS (p = 0.045) in advanced stage HGSOC.

Conclusions: Our results strongly indicate that SLFN11 epigenetic inactivation could be a predictor of resistance to platinum drugs in ovarian cancer. Our results should be further validated in studies based on a larger cohort of patients, in order to further explore whether the DNA methylation of SLFN11 promoter could serve as a potential prognostic DNA methylation biomarker and a predictor of resistance to platinum-based chemotherapy in ovarian cancer.

Keywords: DNA methylation; Schlaffen11; high-grade serous ovarian cancer; liquid biopsy; methylation specific PCR; plasma cell-free DNA; prognostic biomarker; progression free survival.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic flowchart of the study.
Figure 2
Figure 2
(A) DNA methylation of BRCA1, CST6, MGMT, RASSF10, SLFN11 and USP44 gene promoters in primary tumors of patients diagnosed with early (FIGO I-II) and advanced stage (FIGO III) HGSOC. (B) DNA methylation of BRCA1, SLFN11 and USP44 gene promoters in plasma cfDNA of patients diagnosed with advanced (FIGO III) and metastatic stage (FIGO IV) HGSOC.
Figure 3
Figure 3
Kaplan–Meier estimates of patients with advanced HGSOC (FIGO III) in relation to DNA methylation of SLFN11 in plasma cfDNA and PFS (n = 84).
See this image and copyright information in PMC

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