Hypermethylation of Secreted Frizzled Related Protein 1 gene promoter in different astrocytoma grades
Autor: | Antonia Jakovčević, Valentina Karin-Kujundžić, Anja Kafka, Anja Bukovac, Nives Pećina-Šlaus, Ljiljana Šerman, Niko Njirić |
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Rok vydání: | 2018 |
Předmět: |
Adult
Epigenomics Male SFRP1 DNA methylation Wnt signaling astrocytic brain tumors LEF1 TCF1 beta-catenin Lymphoid Enhancer-Binding Factor 1 DNA Mutational Analysis Astrocytoma Biology Malignancy Polymerase Chain Reaction Young Adult 03 medical and health sciences Exon 0302 clinical medicine Basic Science Secreted frizzled-related protein 1 T Cell Transcription Factor 1 medicine Humans Gene silencing Gene Silencing Promoter Regions Genetic neoplasms beta Catenin Aged Brain Neoplasms Membrane Proteins DNA Neoplasm Exons General Medicine DNA Methylation Middle Aged medicine.disease Immunohistochemistry nervous system diseases 030220 oncology & carcinogenesis Cancer research Intercellular Signaling Peptides and Proteins Female 030217 neurology & neurosurgery |
Zdroj: | Croatian Medical Journal Volume 59 Issue 5 |
ISSN: | 1332-8166 0353-9504 |
DOI: | 10.3325/cmj.2018.59.213 |
Popis: | 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. |
Databáze: | OpenAIRE |
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