NHE7 IMPLICATION IN GLIOMA PROGNOSIS: AN <EM>IN SILICO</EM> AND AN <EM>IN VITRO</EM> APPROACH

Gliomas are highly heterogeneous primary brain tumors marked by diffuse infiltration, therapeutic resistance, and dismal prognosis, particularly in high-grade forms. Tumor cell adaptation to hostile microenvironmental conditions critically depends on intracellular pH homeostasis and vesicular trafficking, processes that govern cell motility, invasion, and signal transduction. Na⁺/H⁺ exchangers (NHEs) are central regulators of pH balance in cancer, preventing cytosolic acidification through Na⁺-coupled proton extrusion. While several isoforms, including NHE1, NHE5, and NHE9, have been implicated in glioma biology, the role of the intracellular exchanger NHE7 (SLC9A7), a key regulator of vesicular acidification, remains poorly defined.
To address this knowledge gap, we performed an integrative analysis of NHE7 expression across the TCGA, CGGA693, and CGGA325 cohorts. Across all cohorts, NHE7 expression was consistently reduced in high-grade gliomas relative to low-grade tumors and was significantly associated with decreased overall survival and adverse clinical outcome (HR [95% CI] = 0.650, p < 0.001). Functional enrichment analyses (KEGG and GO) revealed significant alterations in pathways related to exocytosis, calcium signaling, ion channel activity, and neurotransmitter release, implicating NHE7 in vesicle-dependent signaling and intercellular communication.
To translate these observations into functional insight, NHE7 expression is being modulated in IDH-wildtype glioblastoma cell lines (U373, U87-MG, T98G). Ongoing in vitro studies aim to elucidate the mechanistic contribution of NHE7 to the dysregulated pathways identified in silico. Collectively, these findings identify NHE7 as a previously underappreciated regulator of glioma progression and prognosis, and support its further exploration as a mechanistic and therapeutic target in glioblastoma.