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

被引:11
|
作者
Kafka, Anja [1 ,2 ]
Karin-Kujundzic, Valentina [1 ]
Serman, Ljiljana [1 ]
Bukovac, Anja [1 ,2 ]
Njiric, Niko [2 ]
Jakovcevic, Antonia [3 ]
Pecina-Slaus, Nives [1 ,2 ]
机构
[1] Univ Zagreb, Dept Biol, Sch Med, Zagreb, Croatia
[2] Univ Zagreb, Croatian Inst Brain Res, Sch Med, Lab Neurooncol, Salata 12, Zagreb 10000, Croatia
[3] Univ Hosp Ctr Zagreb, Dept Pathol & Cytol, Zagreb, Croatia
关键词
FRIZZLED-RELATED PROTEINS; BETA-CATENIN; SIGNALING PATHWAY; MOLECULAR SUBTYPES; GLIOBLASTOMA CELLS; DNA METHYLATION; WNT INHIBITION; EXPRESSION; ACTIVATION; MECHANISMS;
D O I
10.3325/cmj.2018.59.213
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:213 / 223
页数:11
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