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Methylation-associated silencing of SFRP1 gene in high-grade serous ovarian carcinomas

Vedran Kardum1, Valentina Karin2, Mislav Glibo2

  • 1Department of Obstetrics and Gynecology, University Hospital Merkur, Zagreb, Croatia.

Annals of Diagnostic Pathology
|November 18, 2017
PubMed

Insights

Secreted frizzled-related protein 1 (SFRP1) loss is observed in ovarian cancers. While SFRP1 is unmethylated in low-grade serous ovarian carcinomas (LGSC), its expression is reduced. High-grade serous ovarian carcinomas (HGSC) show SFRP1 hypermethylation and reduced expression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Wnt signaling pathway is crucial for tissue regeneration and stem cell regulation.
  • Aberrant Wnt pathway activation, often due to reduced expression of inhibitors like SFRP1, is implicated in tumorigenesis.
  • SFRP1 acts as a Wnt antagonist, and its dysregulation is observed in various cancers.

Purpose of the Study:

  • To investigate the expression of SFRP1 protein in different grades of ovarian carcinoma.
  • To analyze the methylation status of the SFRP1 gene in ovarian cancer tissues.
  • To explore the correlation between SFRP1 expression, gene methylation, and ovarian cancer subtypes.

Main Methods:

  • Immunohistochemistry was used to assess SFRP1 protein expression in normal ovarian tissues, LGSC, and HGSC.
  • Methylation-specific PCR was employed to analyze SFRP1 gene promoter methylation.
  • Statistical analysis was performed to compare SFRP1 expression levels between groups.

Main Results:

  • SFRP1 gene was unmethylated and protein expression was strong in normal ovarian tissues.
  • SFRP1 gene was largely unmethylated in LGSC, but protein expression was significantly lower than in normal controls.
  • HGSC samples showed SFRP1 gene hypermethylation in 54% of cases, with significantly reduced protein expression compared to normal ovaries.

Conclusions:

  • Loss of SFRP1 protein expression occurs in both LGSC and HGSC, suggesting its role in ovarian tumorigenesis.
  • SFRP1 promoter hypermethylation is a mechanism contributing to SFRP1 loss in a subset of HGSCs.
  • Further research is needed to understand the regulatory mechanisms in LGSC and the clinical/therapeutic implications of SFRP1 alterations in ovarian cancer.
Keywords:
Ovarian serous carcinomaSFRP proteinsSFRP1Wnt pathway

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