4.1 Article

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

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CROATIAN MEDICAL JOURNAL
卷 59, 期 5, 页码 213-223

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MEDICINSKA NAKLADA
DOI: 10.3325/cmj.2018.59.213

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资金

  1. Croatian Science Foundation [6625]
  2. CoRE - Neuro European Regional Development Fund, Operational Programme Competitiveness and Cohesion [KK.01.1.1.01.0007]

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Aim To identify the involvement of Secreted Frizzled Related Protein 1 (SFRP1) promoter (hypermethylation in different malignancy grades of astrocytorn) 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 stereo logical 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 292% 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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