Abstract 3726: Expressions of genes for connexins and Kir5.1 differ between oligodendrogliomas and glioblastomas in patients treated with anticonvulsants
Authors: Marie E. Beckner
Journal: Cancer Research (2020)

Abstract Background: Glia in the CNS buffer potassium ions released by neurons as they fire action potentials. Glial activity occurs at synapses, along axons, and possibly throughout the glial network. Faulty glial potassium buffering can contribute to seizure activity via altered synaptic dynamics. Hypothesis: Contrasting gene expression patterns in glial mediators of potassium buffering are proposed to exist among different types of gliomas. Methods: The REMBRANDT database (12/4/2019, Georgetown Database of Cancer (G-DOC®)) contains 75 glioblastoma and 24 oligodendroglioma patients, treated with anticonvulsants to control seizures, whose tumor gene expressions were determined by reporter probes on microarrays. Differences were found with t-tests, paired via reporter probes when possible. Results: Based on two reporters, KCNJ16 (encodes the Kir5.1 potassium channel) had decreased expression in glioblastomas versus oligodendrogliomas, p=0.014793, 2-tailed. Functionally, Kir5.1 can form heteromeric channels with Kir4.1 to conduct potassium with altered sensitivity to pH. Based on one reporter per gene, three astrocytic-type connexin genes, GJA1(Cx43), GJB2(Cx26) and GJB6(Cx30), as a group, were expressed more so in glioblastomas than in oligodendrogliomas, p=0.047647, 1-tailed. Finding only one oligodendrocytic-type connexin gene with only one reporter probe available in REMBRANDT prevented reverse comparisons. Using two reporters per gene, ATP1A2 (encodes the glial version of Na,K-ATPase alpha) was expressed more than the neuronal version of this transporter (ATP1A1) in glioblastomas and in oligodendrogliomas, p=0.027755 and 0.034492, respectively, 2-tailed, unpaired. Possibly expression of ATP1A1 found at low levels in the gliomas reflects residual neuronal elements. Significant differences between the two types of gliomas were undetectable for many other known and potential glial mediators of potassium buffering using 2 reporter probes each for KCNJ10(Kir4.1), SLC12A2(NKCC1), KCNK3(TASK1), KCNK9(TASK3), SLC12A6(KCC3), KCNA2(Kv1.2), KCNA6(Kv1.6), KCNQ3(Kv7.3), KCNJ13(Kir7.1) &amp; KCNK1(TWIK1), and 4 reporter probes for KCNMA1(BK-alpha1). Several other potassium channels and transporters either have only one reporter available in REMBRANDT or have not been tested yet. No significant differences in the 2 types of gliomas were detected for six house-keeping genes, 3 to 8 reporters per gene. Conclusion: Gene expression patterns for at least some glial potassium buffering mediators differ between glioblastomas and oligodendrogliomas at levels detectable with minimal numbers of reporter probes available for most of the genes encoding potential glial potassium buffering mediators. Potassium buffering mediators in gliomas warrant further investigation. Importantly, the Kir5.1 potassium channel with its sensitivity to pH may play an important functional role that is compromised in gliomas with low expression of this gene. Acknowledgement: The data utilized in this study were provided by the Georgetown Database of Cancer (G-DOC®), a project of the Georgetown Lombardi Comprehensive Cancer Center designed to provide advanced translational research tools to the scientific community. Citation Format: Marie E. Beckner. Expressions of genes for connexins and Kir5.1 differ between oligodendrogliomas and glioblastomas in patients treated with anticonvulsants [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3726.