Expression of KCNN4 in adult-type diffuse gliomas and its correlations with clinicopathological features and patient prognosis

Abstract

BackgroundThe KCa3.1 channel (KCNN4) is extensively investigated as an oncogene in human cancers. The current study aimed to explore the clinicopathological significance of KCNN4 expression in patients with primary adult-type diffuse gliomas. MethodsDemographic, RNA-seq, and follow-up data of 477 patients were retrospectively reviewed. Patients were divided into the experimental and validation groups (278 and 199). KCNN4-related genes were determined by Pearson correlation analysis, and enrichment analyses and tumor-infiltrating immune cell assessments were applied to explore the potential mechanisms of KCNN4 involving glioma progression. The Kaplan-Meier method and the Cox regression analysis were used to evaluate the prognostic value of KCNN4 expression. ResultsKCNN4 showed significantly higher expression level in glioblastoma, IDH-wildtype, followed by astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant and 1p/19q-codeleted (p < 0.001). Enrichment analyses and tumor-infiltrating immune cell assessments suggested that KCNN4 could involve glioma progression through extracellular regulation, affecting immune response, and modulating subcellular trafficking. At last, the Kaplan-Meier analysis showed that high KCNN4 expression was significantly correlated with poor progression-free and overall survival (p < 0.001 for both). While multivariate Cox regression analysis obtained an insignificant result. ConclusionsKCNN4 was identified to be overexpressed in glioma cells and its expression level is positively related to tumor malignancy. It potentially participates in glioma biology by affecting extracellular regulation, subcellular trafficking, and immune escape. Additionally, high KCNN4 expression was correlated with poor survival outcomes of patients. The results can shed new light on the mechanisms of glioma progression, and provide a potential therapeutic target for treating gliomas.