Abstract 2319: Expressions of genes encoding pH-sensitive potassium channels differ between oligodendrogliomas and glioblastomas with potential metabolic effects

Abstract

Abstract 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.