Abstract
PurposeGlioma is the most common primary intracranial tumor. Owing to the poor prognosis associated with high-grade gliomas, there is an urgent need to identify biomarkers related to prognosis and treatment sensitivity. Here, we analyze the expression of FXYD2 mRNA in gliomas, and explore its clinical prognostic value and significance in this disease.MethodsClinical features, FXYD2 mRNA expression levels, and survival data were analyzed for 516 glioma patients from the Chinese Glioma Genome Map Project, 481 from the cancer genome map datbase and 268 from the molecular braintumor database. The expression patterns for FXYD2 mRNA were compared using the chi-square test, and overall survival (OS) of glioma patients was evaluated according to FXYD2 mRNA expression levels. The factors affecting glioma survival were evaluated by Cox univariate and multivariate regression analysis.ResultsFXYD2 mRNA expression was related to the grade of gliomas. The higher the level, the lower the expression. Meanwhile related to the pathological classification of gliomas. Oligodendroglioma, IDH-mutant and 1p/19q-codeleted was higher than Astrocytoma, IDH-mutant, higher than Glioblastoma, IDH-wildtype. Moreover, temozolomide (TMZ) chemotherapy was found to be an independent factor affecting survival in patients with high FXYD2 mRNA expression, but not in patients with low expression.ConclusionFXYD2 mRNA expression represents a new independent factor affecting the survival of glioma patients and may serve as an independent prognostic indicator to predict the sensitivity of gliomas to TMZ.
Highlights
Gliomas, the most common primary malignant tumor of the brain [1], was classified in 2021 by the World Health Organization (WHO) based on histopathology, isocitrate dehydrogenase (IDH) mutation and 1p19qZhou et al BMC Neurology (2021) 21:438 application of high-throughput technology for the molecular classification of gliomas as well as for screening differentially expressed genes and drug resistance genes has become a research hotspot to facilitate the development of corresponding targeted drugs.Na/K-ATPase is an oligomeric transmembrane protein composed of α, β, and γ subunits that functions to maintain the dynamic membrane potential and is associated with many cellular functions as well as the pathogenesis of specific diseases [10]
Clinical features and Sodium/potassium-transporting ATPase subunit gamma (FXYD2) mRNA expression in 516 glioma patients in CGGAClinical features included sex, age, recurrence status, histopathology, WHO grade, IDH mutation status, 1p/19q co-deletion status, methylation of O6 methylguanine DNA methyltransferase (MGMT), radiotherapy history, chemotherapy, and integrated diagnosis according to 2021 WHO classification
FXYD2 mRNA expression was not associated with sex (P = 0.657), age (P = 1.000), methylation of MGMT (P = 0.453) or radiotherapy or chemotherapy history (P = 1.000, P = 0.680, respectively) in glioma patients
Summary
The most common primary malignant tumor of the brain [1], was classified in 2021 by the World Health Organization (WHO) based on histopathology, isocitrate dehydrogenase (IDH) mutation and 1p19qZhou et al BMC Neurology (2021) 21:438 application of high-throughput technology for the molecular classification of gliomas as well as for screening differentially expressed genes and drug resistance genes has become a research hotspot to facilitate the development of corresponding targeted drugs.Na/K-ATPase is an oligomeric transmembrane protein composed of α, β, and γ subunits that functions to maintain the dynamic membrane potential and is associated with many cellular functions as well as the pathogenesis of specific diseases [10]. Na/K-ATPase upregulation has been reported in various cancers [11,12,13,14,15]. Inhibiting Na/K-ATPase activation and expression effectively inhibits cancer cell proliferation and survival [16, 17]. FXYD2 (sodium/ potassium-transporting ATPase subunit gamma) is the γ subunit of the Na/K-ATP enzyme and functions as a regulator of the enzyme activity [18]. A previous study reported that in ovarian clear cell carcinoma (CCC) patients, the expression level of FXYD2 was positively correlated with patient prognosis. Upregulated FXYD2 expression increased the sensitivity of ovarian CCC cells to the Na/K-ATPase inhibitor cardiotonic glycoside, thereby enhancing its therapeutic effect. The expression pattern and clinical significance of FXYD2 have not yet been reported in gliomas
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