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Increased KCNN4 Expression Is Correlated With Poor Survival in Lower Grade Glioma
Steven Lehrer1, Peter H Rheinstein2
1Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A.
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.
Insights
Blocking calcium-activated potassium channel KCa3.1 inhibits glioma cell proliferation and tumor growth. Targeting KCa3.1 may offer a new therapeutic strategy for glioma patients with poor prognoses.
Area of Science:
- Neuro-oncology
- Molecular biology
- Cancer research
Background:
- Glioma networks involve pacemaker cells with pulsing calcium ions, driving tumor growth.
- Calcium-activated potassium channel KCa3.1 plays a role in glioma cell proliferation and network signaling.
Purpose of the Study:
- To investigate the prognostic significance of KCNN4, the gene encoding KCa3.1, in human glioma.
- To evaluate the potential of KCa3.1 inhibitors as a therapeutic strategy for glioma.
Main Methods:
- Analysis of the Cancer Genome Atlas (TCGA) Lower Grade Glioma (LGG) dataset.
- Evaluation of KCNN4 gene expression and copy number variations in relation to patient survival.
- In vitro and in vivo studies using KCa3.1 inhibitors to assess effects on glioma cell viability and tumor growth.
Main Results:
- High KCNN4 expression is associated with unfavorable survival in human glioma.
- KCNN4 copy number variations, particularly increased masked copy number segments, are also prognostic.
- KCNN4 loss in 1p 19q co-deleted gliomas correlates with a more favorable prognosis.
Conclusions:
- Increased KCNN4 expression is linked to poor survival in lower grade glioma.
- KCa3.1-inhibiting drugs represent a potential therapeutic avenue for glioma treatment.
- Targeting KCa3.1 could be beneficial for patients with high KCNN4 expression.
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