TMEM165 promotes glioblastoma progression through epithelial-mesenchymal transition-mediated invasion and temozolomide chemoresistance.

Gliomas are the most common primary malignant tumors of the central nervous system and are characterized by their highly aggressive nature and poor prognosis. This study elucidates the oncogenic role of transmembrane protein TMEM165 in glioblastoma and its therapeutic potential. Bioinformatics analysis revealed that high expression of N-linked glycosylation regulatory proteins predicts poor prognosis in glioma patients, with TMEM165 first reported here demonstrating significant associations with shorter survival, higher tumor grade, and IDH wild-type status. Enrichment analysis indicated activation of the epithelial-mesenchymal transition (EMT) pathway in TMEM165-high groups and a positive correlation with temozolomide (TMZ) resistance. In vivo and in vitro experiments demonstrated that TMEM165 promotes glioblastoma proliferation, migration, and invasion by modulating EMT-related proteins, while reducing its sensitivity to TMZ. These findings identify TMEM165 as a novel therapeutic target for glioblastoma.