Integrative analysis defines DDIT3 amplification as a correlative and essential factor for glioma malignancy.

Glioma, particularly glioblastoma multiforme (GBM), is a highly aggressive and lethal primary brain tumor with poor prognosis. Metabolic reprogramming and endoplasmic reticulum (ER) stress are two crucial factors contributing to glioma pathogenesis. However, the intricate coordination between these processes remains incompletely understood. Here, we conducted an integrative analysis to elucidate the nodal role of DNA Damage Inducible Transcript 3 (DDIT3) to couple metabolisms and stress responses in glioma. We demonstrated a positive association between DDIT3 amplification/enhanced expression with glioma malignancy, indicating its potential as a novel biomarker for prognosis and treatment stratification. Genomic and transcriptomic analyses further revealed the involvement of DDIT3 enhancement in glioma progression. Moreover, immune infiltration analysis showed that distinct DDIT3 expression groups had different immune microenvironment. Finally, validations confirmed the impact of DDIT3 on proliferation and migration of glioma cells. Our findings provide novel insights into the complex interplay between metabolic reprogramming and ER stress, and defines DDIT3 as a promising therapeutic target in glioma.