Chehade Georges, El Hajj Nady, Aittaleb Mohamed, Alkailani Maisa I, Bejaoui Yosra, Mahdi Asma, Aldaalis Arwa A H, Verbiest Michael, Lelotte Julie, Ruiz-Reig Nuria, Durá Irene, Raftopoulos Christian, Tajeddine Nicolas, Tissir Fadel
Université Catholique de Louvain, Institute of Neuroscience, Cellular and Molecular Division, Brussels, Belgium.
College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
Front Oncol. 2024 Feb 22;14:1359652. doi: 10.3389/fonc.2024.1359652. eCollection 2024.
Glioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the 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 methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors.
We analyzed 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 expression, explored the relationship between mRNA levels and Patient's survival after the surgical resection. Finally, we assessed the methylation pattern of the promoter using a targeted deep bisulfite sequencing approach.
We found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in , respectively. We scrutinized the expression of at single cell level and detected an overlap with expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed expression in our cohort and uncovered a positive correlation between mRNA level and patient's survival. The effect of was prominent in -methylated glioblastoma. Finally, we report that the expression of is at least partially regulated by the methylation of three CpG sites in the promoter region.
We propose that combining the expression with methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with -methylated glioblastoma.
胶质母细胞瘤是最具侵袭性的原发性脑肿瘤之一，尽管采用了多模式治疗，但其预后仍然很差。启动子甲基化可预测对替莫唑胺的反应，是胶质母细胞瘤公认的预后标志物。然而，在甲基化组内仍可检测到生存差异，一些患者的生存期比其他患者短，这强调了需要其他预测因素。
我们分析了癌症基因组图谱（TCGA）中胶质母细胞瘤样本的表达情况。我们还回顾性分析了2013年5月至2019年8月在圣卢大学医院接受手术的117例组织学胶质母细胞瘤患者。我们分析了表达情况，探讨了mRNA水平与手术切除后患者生存之间的关系。最后，我们使用靶向深度亚硫酸氢盐测序方法评估了启动子的甲基化模式。
我们发现，分别有36%和1%的TCGA胶质母细胞瘤样本在中表现出拷贝数改变和突变。我们在单细胞水平上仔细研究了的表达，并检测到与胶质母细胞瘤增殖细胞中的表达存在重叠，包括神经祖细胞样、少突胶质细胞祖细胞样和星形胶质细胞样状态。我们定量分析了我们队列中的表达情况，发现mRNA水平与患者生存之间存在正相关。在甲基化的胶质母细胞瘤中，的作用尤为突出。最后，我们报告的表达至少部分受启动子区域三个CpG位点甲基化的调控。
我们建议，将的表达与甲基化相结合，可以为甲基化的胶质母细胞瘤患者提供更好的生存预测和更合适的术后治疗。
