Abstract 2319: Expressions of genes encoding pH-sensitive potassium channels differ between oligodendrogliomas and glioblastomas with potential metabolic effects
Authors: Beckner Marie E. 
Published: July 2021

Potassium, the major intracellular cation, is released by neurons as they fire action potentials. Glial cells take up released K+ ions and later return them. Faulty glial K+ buffering contributes to seizures. Previously, in brain tumor patients treated with anticonvulsants, KCNJ16 (Kir5.1 K+ channel) had decreased expression (p=0.014793) in 75 glioblastomas vs. 24 oligodendrogliomas (18.78 & 50.77 mo. survival, respectively) (Beckner, Expressions of genes for connexins & Kir5.1 differ between oligodendrogliomas & glioblastomas in patients treated with anticonvulsants. Proceedings of 111 AACR Meeting, 2020, Abst#3726). Kir5.1 forms heteromeric channels with Kir4.1 (major glial K+ channel without energy requirement) to provide sensitivity to acidosis. Loss of Kir5.1 renders cells retaining Kir4.1 resistant to acidosis.

Hypothesis: Gene expressions for multiple pH-sensitive K+ channels are altered between tumor types. Also, because K+ may associate with toxic byproducts of glycolysis, expression of GLO1 & 2, genes for glyoxalases, differ between tumor types. The REMBRANDT database (11/17/2020, Georgetown Database of Cancer (G-DOC®)) contains 220 glioblastoma & 67 oligodendroglioma patients with microarray gene expressions determined by reporter probes (1-3/gene of interest). Of these, 75 glioblastoma & 24 oligodendroglioma patients were treated with anticonvulsants. 2-tailed t-tests, paired via reporters, were performed. Expression of KCNJ16 (2 reporters), was decreased in 220 glioblastomas vs. 67 oligodendrogliomas, p=0.05004. Therefore, tumor patients treated with anticonvulsants showed a greater decrease in KCNJ16 expression in glioblastomas. They also had decreased expression (p=0.05158) of combined KCNK2(TREK1, 1 reporter) & KCNK10(TREK2, 3 reporters) and trends for decreased expressions of KCNK10(TREK2) alone (p=0.10462) & KCNK9 (TASK3) (p=0.21802), & increased expression of KCNK3 (TASK1) (p=0.20019). Glioblastomas had a trend for decreased combined expression (p=0.20504) of glyoxalase genes (GLO1 & GLO2, 1 reporter each). House-keeping genes, 3-8 reporters/gene, did not differ.

Conclusion: Gene expressions show trends & significant differences among pH sensitive K+ channels in glioblastomas vs. oligodendrogliomas. Decreased expression of glyoxalases in glioblastomas, consistent with buildup of toxic glycolytic byproducts, highlights the importance of altered tumor cell K+ channeling. Loss of Kir5.1's modulation of Kir4.1 (primary non-ATP dependent glial K+ channel) resulting in putative anomalous K+ uptake may mitigate effects of toxic glycolytic byproducts in acidosis.

Acknowledgement: Data were provided by the Georgetown Database of Cancer (G-DOC®), a project of the Georgetown Lombardi Comprehensive Cancer Center to provide advanced translational research tools to the scientific community.

Citation Format: Marie E. Beckner. Expressions of genes encoding pH-sensitive potassium channels differ between oligodendrogliomas and glioblastomas with potential metabolic effects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2319.