Wnt pathway antagonists, SFRP1, SFRP2, SOX17, and PPP2R2B, are methylated in gliomas and SFRP1 methylation predicts shorter survival.
The deregulation of Wnt signaling is observed in various cancers, including gliomas, and might be related to the methylation of the genes encoding antagonists of this signaling pathway. The aim of the study was to assess the methylation status of the promoter regions of six Wnt negative regulators and to determine their prognostic value in clinical samples of gliomas of different grades. The methylation of SFRP1, SFRP2, PPP2R2B, DKK1, SOX17, and DACH1 was analyzed in 64 glioma samples using methylation-specific polymerase chain reaction (MSP). The results were analyzed in correlation with clinicopathological data. Promoter methylation in at least one of the analyzed genes was found in 81.3 % of the tumors. All benign tumors [grade I according to the World Health Organization (WHO) classification] lacked the methylation of the studied genes, whereas grade II, III, and IV tumors were, in most cases, methylation-positive. The methylation index correlated with the patient's age. The most frequently methylated genes were SFRP1 and SFRP2 (73.4 % and 46.9 %, respectively), followed by SOX17 (20.3 %) and PPP2R2B (10.9 %); DKK1 and DACH1 were basically unmethylated (1.6 %). SFRP1 methylation negatively correlated with patients' survival time, and was significantly more frequent in older patients and those with higher grade tumors. Overall, the results of this study indicate that aberrant promoter methylation of Wnt pathway antagonists is common in gliomas, which may be the possible cause of up-regulation of this signaling pathway often observed in these tumors. Moreover, SFRP1 promoter methylation can be regarded as a potential indicator of glioma patients' survival.
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Poznań, Poland.
Aleksandra
A
Majchrzak-Celińska
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Poznań, Poland.
Marta
M
Słocińska
Department and Clinic of Neurosurgery and Neurotraumatology, Poznan University of Medical Sciences, Poznań, Poland.
Anna-Maria
AM
Barciszewska
Department and Clinic of Neurosurgery and Neurotraumatology, Poznan University of Medical Sciences, Poznań, Poland.
Stanisław
S
Nowak
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Poznań, Poland. baerw@man.poznan.pl.
Wanda
W
Baer-Dubowska
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D054648:Protein Phosphatase 2 / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D055760:SOXF Transcription Factors / Q000235:genetics; D015996:Survival Rate; D060449:Wnt Signaling Pathway; D055815:Young Adult; D000099274:Frizzled-Related Proteins; D000094742:Secreted Frizzled-Related Proteins
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D054648:Protein Phosphatase 2; D011506:Proteins; D055760:SOXF Transcription Factors; D000099274:Frizzled-Related Proteins; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C109188:SOX17 protein, human; C505936:PPP2R2B protein, human
DNA methylation; PPP2R2B; SFRP1; SFRP2; SOX17; Wnt pathway