HBQ1 Acts as a Prognostic Biomarker and Tumor Suppressor Linked to Antigen Presentation in Glioma

ABSTRACT Glioma is a highly aggressive brain tumor associated with substantial morbidity and mortality and with limited treatment options. This study investigates the functional role of Hemoglobin Subunit Theta 1 (HBQ1) in glioma and evaluates its potential as a prognostic biomarker. Using integrated bioinformatics approaches, we demonstrated that HBQ1 expression was significantly downregulated in glioma tissues compared to normal brain tissues and was inversely correlated with tumor grade. Survival analysis indicated that lower HBQ1 expression is associated with poorer overall survival and disease‐free survival. Functional enrichment analyses connected HBQ1 to key pathways including antigen presentation (MHC II), calcium signaling, mitogen‑activated protein kinase (MAPK) signaling, and γ‑aminobutyric acid (GABA)‑ergic synapse. In vitro , overexpression of HBQ1 in U87 cells markedly suppressed proliferation, migration, and invasion, while enhancing antigen presentation. Moreover, HBQ1 expression was significantly correlated with important molecular markers such as isocitrate dehydrogenase (IDH) mutation, 1p/19q co‐deletion, and O6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation, as well as with genes involved in glutamate‐GABA metabolism. Collectively, our findings identify HBQ1 as a novel prognostic biomarker and a potential tumor suppressor in glioma, possibly through modulating the immune microenvironment and neuron–glioma crosstalk.