DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma
BackgroundGlioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1359652/full |
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| author | Georges Chehade Nady El Hajj Mohamed Aittaleb Maisa I. Alkailani Yosra Bejaoui Asma Mahdi Arwa A. H. Aldaalis Michael Verbiest Julie Lelotte Nuria Ruiz-Reig Irene Durá Christian Raftopoulos Nicolas Tajeddine Fadel Tissir Fadel Tissir |
| author_facet | Georges Chehade Nady El Hajj Mohamed Aittaleb Maisa I. Alkailani Yosra Bejaoui Asma Mahdi Arwa A. H. Aldaalis Michael Verbiest Julie Lelotte Nuria Ruiz-Reig Irene Durá Christian Raftopoulos Nicolas Tajeddine Fadel Tissir Fadel Tissir |
| author_sort | Georges Chehade |
| collection | DOAJ |
| description | BackgroundGlioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT 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 MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors.MethodsWe analyzed DIAPH3 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 DIAPH3 expression, explored the relationship between mRNA levels and Patient’s survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach.ResultsWe found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 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 DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient’s survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region.ConclusionWe propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma. |
| first_indexed | 2024-03-07T23:04:47Z |
| format | Article |
| id | doaj.art-1369f93b831e4ee098f1f9224cf0cca6 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-07T23:04:47Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-1369f93b831e4ee098f1f9224cf0cca62024-02-22T05:19:18ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-02-011410.3389/fonc.2024.13596521359652DIAPH3 predicts survival of patients with MGMT-methylated glioblastomaGeorges Chehade0Nady El Hajj1Mohamed Aittaleb2Maisa I. Alkailani3Yosra Bejaoui4Asma Mahdi5Arwa A. H. Aldaalis6Michael Verbiest7Julie Lelotte8Nuria Ruiz-Reig9Irene Durá10Christian Raftopoulos11Nicolas Tajeddine12Fadel Tissir13Fadel Tissir14Université Catholique de Louvain, Institute of Neuroscience, Cellular and Molecular Division, Brussels, BelgiumCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, QatarCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, QatarCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, QatarCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, QatarCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, QatarCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, QatarLaboratory of Population Genomics, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Neuropathology, Saint-Luc University Hospital, Brussels, BelgiumUniversité Catholique de Louvain, Institute of Neuroscience, Cellular and Molecular Division, Brussels, BelgiumUniversité Catholique de Louvain, Institute of Neuroscience, Cellular and Molecular Division, Brussels, BelgiumDepartment of Neurosurgery, Saint-Luc University Hospital, Brussels, BelgiumUniversité Catholique de Louvain, Institute of Neuroscience, Cellular and Molecular Division, Brussels, BelgiumUniversité Catholique de Louvain, Institute of Neuroscience, Cellular and Molecular Division, Brussels, BelgiumCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, QatarBackgroundGlioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT 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 MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors.MethodsWe analyzed DIAPH3 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 DIAPH3 expression, explored the relationship between mRNA levels and Patient’s survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach.ResultsWe found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 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 DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient’s survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region.ConclusionWe propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma.https://www.frontiersin.org/articles/10.3389/fonc.2024.1359652/fulldiaphanous forminglioblastomamDia2O(6)-methylguanine-DNA methyltransferaseMGMT methylationsurvival |
| spellingShingle | Georges Chehade Nady El Hajj Mohamed Aittaleb Maisa I. Alkailani Yosra Bejaoui Asma Mahdi Arwa A. H. Aldaalis Michael Verbiest Julie Lelotte Nuria Ruiz-Reig Irene Durá Christian Raftopoulos Nicolas Tajeddine Fadel Tissir Fadel Tissir DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma Frontiers in Oncology diaphanous formin glioblastoma mDia2 O(6)-methylguanine-DNA methyltransferase MGMT methylation survival |
| title | DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma |
| title_full | DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma |
| title_fullStr | DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma |
| title_full_unstemmed | DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma |
| title_short | DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma |
| title_sort | diaph3 predicts survival of patients with mgmt methylated glioblastoma |
| topic | diaphanous formin glioblastoma mDia2 O(6)-methylguanine-DNA methyltransferase MGMT methylation survival |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1359652/full |
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