TMEM2 Combined with IDH and 1p19q in Refining Molecular Subtypes for Predicting Survival of Patients with Glioma

Gliomas are common intracranial tumors with high morbidity and mortality in adults. Transmembrane protein 2 (TMEM2) is involved in the malignant behavior of solid tumors. TMEM2 regulates cell adhesion and metastasis as well as intercellular communication by degrading nonprotein components of the extracellular matrix. This study aimed to evaluate the relationship between TMEM2 expression levels and glioma subtypes or patient prognosis. Our findings revealed that TMEM2 expression was abnormally upregulated in high-grade glioma. Moreover, combining TMEM2, the status of isocitrate dehydrogenase (IDH) and 1p19q, we subdivided molecular subtypes with significant differences in survival. Patients in the MT-codel-low subgroup had better prognosis than those in the WT-no-codel-high subgroup, who fared the worst. Additionally, correlation analysis of TMEM2 and immune cell infiltration indicated an altered tumor microenvironment (TME) and cell redistribution in the TMEM2 high-expression subtype. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that focal adhesion and PI3K-Akt signaling pathways were enriched in the TMEM2-expressing group. In conclusion, aberrant TMEM2 expression can be used as an independent prognostic marker for refining glioma molecular subtyping and accurate prognosis. These findings will improve rational decision making to provide individualized therapy for patients with glioma.