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

Kafka, Anja and Karin-Kujundžić, Valentina and Šerman, Ljiljana and Bukovac, Anja and Njirić, Niko and Jakovčević, Antonia and Pećina-Šlaus, Nives (2018) Hypermethylation of Secreted Frizzled Related Protein 1 gene promoter in different astrocytoma grades. Croatian Medical Journal, 59 (5). pp. 213-223. ISSN 0353-9504

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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.

Item Type: Article
MeSH: 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
Departments: Hrvatski institut za istraživanje mozga
Katedra za medicinsku biologiju
Depositing User: Anja Majstorović
Status: Published
Karin-Kujundžić, ValentinaUNSPECIFIED
Šerman, LjiljanaUNSPECIFIED
Jakovčević, AntoniaUNSPECIFIED
Pećina-Šlaus, NivesUNSPECIFIED
Date: 31 October 2018
Date Deposited: 04 Apr 2019 10:02
Last Modified: 08 Apr 2019 11:20
Subjects: /
Related URLs:
URI: http://medlib.mef.hr/id/eprint/3213

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