Correlation of epigenetic markers with glioblastoma patients' survival and molecular subtypes: insights from methylation-specific MLPA analysis
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Embargo End Date
ICR Authors
Authors
Trabelsi, S
Amara, A
Chabchoub, I
Ladib, M
Krifa, H
Mama, N
Tlili, K
Mokni, M
Yaacoubi, MT
Jones, C
Popov, S
Saad, A
H'mida Ben Brahim, D
Amara, A
Chabchoub, I
Ladib, M
Krifa, H
Mama, N
Tlili, K
Mokni, M
Yaacoubi, MT
Jones, C
Popov, S
Saad, A
H'mida Ben Brahim, D
Document Type
Journal Article
Date
2026-02-06
Date Accepted
Abstract
<jats:title>Abstract</jats:title>
<jats:sec id="j_tjb-2024-0243_abs_001">
<jats:title>Objectives</jats:title>
<jats:p>Glioblastoma (GB) is a heterogeneous group of tumors with poor patient’s outcome. The epigenetic markers could influence patient’s outcome and add more precision in sub-typing.</jats:p>
</jats:sec>
<jats:sec id="j_tjb-2024-0243_abs_002">
<jats:title>Methods</jats:title>
<jats:p>The study aims to determine a correlation between the methylation status of 65 genes and the overall survival (OS) in 50 GB Tunisian patients using methylation specific-multiplex ligation-dependent probe amplification (MS-MLPA) technique.</jats:p>
</jats:sec>
<jats:sec id="j_tjb-2024-0243_abs_003">
<jats:title>Results</jats:title>
<jats:p>
OS was significantly longer for patients with tumors harboring unmethylated tumor suppressor genes
<jats:italic>ATM</jats:italic>
,
<jats:italic>BRCA1</jats:italic>
,
<jats:italic>BRCA2</jats:italic>
,
<jats:italic>TP53</jats:italic>
and
<jats:italic>TP73</jats:italic>
and the DNA repairing gene
<jats:italic>MSH6</jats:italic>
. Furthermore, simultaneous unmethylation of
<jats:italic>ATM</jats:italic>
,
<jats:italic>BRCA2</jats:italic>
,
<jats:italic>CD44</jats:italic>
and
<jats:italic>VHL</jats:italic>
genes was associated with GB presenting normal
<jats:italic>EGFR</jats:italic>
status. This subgroup exhibits a better prognosis (OS=15 months, p=0.005). Our results also showed that, combined methylation of
<jats:italic>TP73</jats:italic>
,
<jats:italic>THBS1</jats:italic>
,
<jats:italic>GSTP1</jats:italic>
and
<jats:italic>ESR1</jats:italic>
genes in amplified
<jats:italic>EGFR</jats:italic>
GB subtype resulted in a poor prognosis group (OS=3 months, p=0.041). Simultaneous methylation of
<jats:italic>HLTF</jats:italic>
and
<jats:italic>SFRP5</jats:italic>
genes was associated with wild-type
<jats:italic>IDH1</jats:italic>
GB defining therefore a very poor prognosis group (OS=1 month, p=0.026). Besides,
<jats:italic>BRCA1</jats:italic>
methylation in wild-type
<jats:italic>IDH1</jats:italic>
group was significantly associated with poor prognosis (OS=6 months, p=0.002). Interestingly,
<jats:italic>RBM14</jats:italic>
and
<jats:italic>PCCA</jats:italic>
genes were co-methylated in 80 % of prolonged survival cases (GB+). In absence of
<jats:italic>EGFR</jats:italic>
amplification and with unmethylation of
<jats:italic>BRCA1</jats:italic>
,
<jats:italic>BRCA2</jats:italic>
,
<jats:italic>ATM</jats:italic>
,
<jats:italic>VHL</jats:italic>
,
<jats:italic>CD44</jats:italic>
,
<jats:italic>HLTF</jats:italic>
and
<jats:italic>SFRP5</jats:italic>
genes, GB+ tumors seemed to respond better to treatment, avoiding the relapse and conferring prolonged survival (>36 months).
</jats:p>
</jats:sec>
<jats:sec id="j_tjb-2024-0243_abs_004">
<jats:title>Conclusion</jats:title>
<jats:p>
Combining genes methylation status of GB with
<jats:italic>EGFR</jats:italic>
and
<jats:italic>IDH1</jats:italic>
profiles will refine subtyping, predict patient’s outcomes and guide personalized therapy.
</jats:p>
</jats:sec>
Citation
Turkish Journal of Biochemistry, 2026,
Source Title
Turkish Journal of Biochemistry
Publisher
WALTER DE GRUYTER GMBH
ISSN
0250-4685
eISSN
1303-829X
Collections
Research Team
Glioma Team