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. 2018 Oct 31;59(5):213-223.
doi: 10.3325/cmj.2018.59.213.

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

Anja Kafka, Valentina Karin-Kujundžić, Ljiljana Šerman, Anja Bukovac, Niko Njirić, Antonia Jakovčević, Nives Pećina-Šlaus  1
Affiliations

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

Anja Kafka et al. Croat Med J. .

Abstract

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.

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Figures

Figure 1
Figure 1
Methylation-specific polymerase-chain-reaction analysis for Secreted Frizzled Related Protein 1 (SFRP1) gene promoter in astrocytic brain tumors (A) grade II (1AII-6AII); (B) grade III (1AIII-6AIII); and (C) grade IV (1GIV-13GIV). The presence of a visible polymerase chain reaction product (band) in gel lanes marked U indicates the presence of unmethylated promotors; the product presence in lanes marked M indicates the presence of methylated promotors. Methylated human control (MC) was used as positive control for methylated reaction, human white blood cell DNA (WBC) was used as positive control for unmethylated reaction, and water was used as negative control.
Figure 2
Figure 2
Characteristic immunohistochemical staining of Secreted Frizzled Related Protein 1 (SFRP1) expression in astrocytoma. (A) Negative control; (B) astrocytic brain tumor grade II showing strong cytoplasmic staining; (C) astrocytic brain tumor grade IV (glioblastoma) showing strong cytoplasmic staining (both B and C with unmethylated promoters of SFRP1 gene); (D) astrocytic brain tumor grade IV (glioblastoma) with methylated promoter of SFRP1 gene showing lack of expression.
See this image and copyright information in PMC

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