Increased KCNN4 Expression Is Correlated With Poor Survival in Lower Grade Glioma

Background/Aim: Networks of glioma cells are linked to small groups of pacemaker cells in which levels of calcium ions pulse periodically, driving a signal through the network that causes tumor growth. Using inhibitors, one study blocked the activity of the Ca2+ activated potassium-channel protein KCa3.1 in in vitro models and mice, preventing the proliferation of glioma cells and tumor expansion. Marked reduction of tumor cell viability occurred within the entire network, as well as reduced tumor growth in mice and extended animal survival. Materials and Methods: KCa3.1 is encoded by the gene potassium calcium-activated channel subfamily N member 4 (KCNN4) on the chromosomal location 19q13.31. We used the Cancer Genome Atlas (TCGA) to evaluate the effect of KCNN4 on human glioma survival in the TCGA Lower Grade Glioma (LGG) dataset. Results: In humans, KCNN4 is prognostic in glioma; high expression is unfavorable. In addition, KCNN4 copy number variations are prognostic. Increased masked copy number segments are unfavorable in lower grade glioma. KCNN4 is lost in gliomas with the 1p 19q co-deletion, which may explain in part the comparatively favorable prognosis of 1p 19q co-deletion tumors. Conclusion: Our finding of increased KCNN4 expression related to poor survival in human lower grade glioma suggests that developing novel therapies, such as KCa3.1-inhibiting drugs, might be worthwhile.