关键词: CD47 IDH mutant MGMT methylation TIGIT adult-type diffuse glioma pTERT mutation

Mesh : Adult Humans Brain Neoplasms / pathology CD47 Antigen / genetics Glioma / pathology Glioblastoma / genetics Astrocytoma Prognosis DNA Modification Methylases / genetics Tumor Suppressor Proteins / genetics DNA Repair Enzymes / genetics Receptors, Immunologic / genetics

来  源:   DOI:10.3389/fimmu.2024.1323307   PDF(Pubmed)

Abstract:
In 2021, the World Health Organization published a new classification system for central nervous system tumors. This study reclassified the adult diffuse glioma (ADG) into astrocytoma, oligodendroglioma, and glioblastoma (GBM) according to the new tumor classification.
The association of TERT promoter (pTERT) mutation, MGMT methylation, and CD47/TIGIT expression with patient prognosis was investigated.
Immunohistochemical analysis showed that the expression levels of CD47 and TIGIT in tumor tissues were significantly higher than those in normal brain tissues. CD47 levels were higher in GBM and grade 4 astrocytoma tissues. TIGIT expression was also higher in patients with GBM. The high expressions of CD47, TIGIT, and CD47/TIGIT were positively correlated with MGMT unmethylation but not pTERT mutation. Moreover, MGMT unmethylation was associated with poor overall survival in astrocytoma. High CD47, TIGIT, and CD47/TIGIT levels were associated with significantly reduced survival in ADG and GBM. GBM, MGMT unmethylation, and high CD47 expression were independent prognostic factors for overall survival in ADG.
Collectively, these results showed that the MGMT unmethylation and high levels of CD47 and TIGIT are associated with a poor prognosis in ADG. Patients with high CD47 and TIGIT expression may benefit from anti-CD47 and TIGIT immunotherapy.
摘要:
2021年,世界卫生组织发布了针对中枢神经系统肿瘤的新分类系统。本研究将成人弥漫性胶质瘤(ADG)重新分类为星形细胞瘤,少突胶质细胞瘤,根据新的肿瘤分类和胶质母细胞瘤(GBM)。
TERT启动子(pTERT)突变的关联,MGMT甲基化,和CD47/TIGIT表达与患者预后的关系进行了研究。
免疫组化分析表明,肿瘤组织中CD47和TIGIT的表达水平明显高于正常脑组织。GBM和4级星形细胞瘤组织中CD47水平较高。GBM患者的TIGIT表达也较高。CD47、TIGIT、CD47/TIGIT与MGMT未甲基化呈正相关,但与pTERT突变无关。此外,MGMT未甲基化与星形细胞瘤总体生存率低相关。高CD47,TIGIT,CD47/TIGIT水平与ADG和GBM患者生存率显著降低相关。GBM,MGMT非甲基化,CD47高表达是ADG患者总生存期的独立预后因素。
集体,这些结果表明MGMT的非甲基化和高水平的CD47和TIGIT与ADG的不良预后相关。具有高CD47和TIGIT表达的患者可受益于抗CD47和TIGIT免疫疗法。
公众号