biostudies-literatureChehade GHamad Bin Khalifa UniversityFonds De La Recherche Scientifique - FNRSQatar National Research FundFondation contre le Cancer1359652https://www.ebi.ac.uk/biostudies/studies/S-EPMC10917989biostudies-literatureUnknown14<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 <i>MKI67</i> 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.<h4>Conclusion</h4>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.Frontiers in oncologyDIAPH3 predicts survival of patients with <i>MGMT</i>-methylated glioblastoma.PMC10917989PDR T0236.20, CDR J.0175.23, 0913351 _excellence of ScienceRuiz-Reig NAittaleb MDura IBejaoui YVerbiest MTissir FRaftopoulos CAlkailani MIMahdi AChehade GLelotte JTajeddine NEl Hajj NAldaalis AAHfalseDIAPH3 predicts survival of patients with <i>MGMT</i>-methylated glioblastoma.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 <i>MKI67</i> 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.<h4>Conclusion</h4>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.2024-01-01T00:00:00Z20242026-06-12T03:20:19.699Z2025-04-04T12:35:08.965ZS-EPMC109179893845492910.3389/fonc.2024.1359652