Hypermethylation of Secreted Frizzled Related Protein 1 gene promoter in different astrocytoma grades

Scientific paper - Original scientific paper

• Author: Anja Kafka
• Author: Valentina Karin-Kujundžić
• Author: Ljiljana Šerman
• Author: Anja Bukovac
• Author: Niko Njirić
• Author: Antonia Jakovčević
• Author: Nives Pećina-Šlaus
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences

Abstract (english)

Aim: To identify the involvement of Secreted Frizzled Related Protein 1 (SFRP1) promoter hypermethylation in different malignancy grades of astrocytoma and assess its association with beta-catenin, lymphoid-enhancer factor 1, and T-cell factor 1. Methods: Twenty-six astrocytoma samples were collected from 2008-2015. Promoter hypermethylation was evaluated by methylation-specific polymerase-chain-reaction and protein expression by immunohistochemistry and stereological analysis. The staining intensity was scored by comparing immunoreactivity with normal tissue and by using 10% and 50% cut-offs. Results: SFRP1 promoter methylation was found in 32% of astrocytomas. The number of hypermethylated samples increased in higher astrocytoma grades and was the highest in glioblastoma (P = 0.042 compared to other astrocytoma grades). There was 45.8% of samples with the lack of or weak expression of SFRP1 protein and 29.2% with strong expression. Samples with methylated promoter expressed significantly less SFRP1 than samples with unmethylated promoter (P = 0.031). Beta-catenin expression levels were elevated. Yet, glioblastomas with unmethylated SFRP1 promoter had significantly less beta-catenin (P = 0.033). Strong expression of lymphoid-enhancer factor 1 was associated to higher astrocytoma grades (P = 0.006).
Conclusion: SFRP1 gene was epigenetically silenced in glioblastomas when compared to low astrocytoma grades, which may suggest that the lack of its protein is involved in astrocytoma progression.

• Keywords (english): Adult; Aged; Astrocytoma/genetics; Astrocytoma/pathology; Brain Neoplasms/genetics; Brain Neoplasms/pathology; DNA Methylation; DNA Mutational Analysis; DNA, Neoplasm/genetics; Epigenomics; Exons; Female; Gene Silencing; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins/genetics; Lymphoid Enhancer-Binding Factor 1/genetics; Male; Membrane Proteins/genetics; Middle Aged; Polymerase Chain Reaction; Promoter Regions, Genetic; T Cell Transcription Factor 1/genetics; Young Adult; beta Catenin/genetics
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Croatian Medical Journal
• Numbering: vol. 59, no. 5, pp. 213-223
• p-ISSN: 0353-9504
• DOI: https://doi.org/10.3325/cmj.2018.59.213
• URN:NBN: urn:nbn:hr:105:300029
• Publication: 2018-10-31
• Document URL: https://doi.org/10.3325/cmj.2018.59.213
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 09:47:56