AUTHOR=Ma Lingbo , Shi Yi , Li Chang , Deng Bin , Jiang Jinfang , Cao Yuwen , Wang Lianghai , Li Hongyan 

TITLE=MGMT unmethylation and high levels of CD47 and TIGIT indicate a poor prognosis in adult diffuse gliomas

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1323307

DOI=10.3389/fimmu.2024.1323307

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>The association of TERT promoter (pTERT) mutation, MGMT methylation, and CD47/TIGIT expression with patient prognosis was investigated.</p></sec><sec><title>Results</title><p>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 <italic>MGMT</italic> unmethylation but not p<italic>TERT</italic> mutation. Moreover, <italic>MGMT</italic> 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, <italic>MGMT</italic> unmethylation, and high CD47 expression were independent prognostic factors for overall survival in ADG.</p></sec><sec><title>Discussion</title><p>Collectively, these results showed that the <italic>MGMT</italic> 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.</p></sec>