DIAPH3 predicts survival of patients with <i>MGMT</i>-methylated glioblastoma
<h3>Background</h3><p dir="ltr">Glioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the <i>MGMT</i> promoter, which predicts the response to temozolomide, is a well-established progn...
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2024
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| Summary: | <h3>Background</h3><p dir="ltr">Glioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the <i>MGMT</i> promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the <i>MGMT</i> methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors.</p><h3>Methods</h3><p dir="ltr">We analyzed <i>DIAPH3</i> expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the<i> DIAPH3</i> expression, explored the relationship between mRNA levels and Patient’s survival after the surgical resection. Finally, we assessed the methylation pattern of the <i>DIAPH3</i> promoter using a targeted deep bisulfite sequencing approach.</p><h3>Results</h3><p dir="ltr">We found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in <i>DIAPH3</i>, respectively. We scrutinized the expression of <i>DIAPH3</i> at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed <i>DIAPH3</i> expression in our cohort and uncovered a positive correlation between <i>DIAPH3</i> mRNA level and patient’s survival. The effect of <i>DIAPH3</i> was prominent in <i>MGMT</i>-methylated glioblastoma. Finally, we report that the expression of <i>DIAPH3</i> is at least partially regulated by the methylation of three CpG sites in the promoter region.</p><h3>Conclusion</h3><p dir="ltr">We propose that combining the <i>DIAPH3</i> expression with <i>MGMT</i> methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with <i>MGMT</i>-methylated glioblastoma.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Oncology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fonc.2024.1359652" target="_blank">https://dx.doi.org/10.3389/fonc.2024.1359652</a></p> |
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