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. 2023 May;50(5):4285-4299.
doi: 10.1007/s11033-023-08371-y. Epub 2023 Mar 14.

SLC12A5 as a novel potential biomarker of glioblastoma multiforme

Jiakai Chen  1 , Handong Wang  2 , Chulei Deng  3 , Maoxing Fei  4
Affiliations

SLC12A5 as a novel potential biomarker of glioblastoma multiforme

Jiakai Chen et al. Mol Biol Rep. 2023 May.

Abstract

Background: Glioblastoma multiforme (GBM) is the most prevalent and malignant intracranial tumor with significant features of dismal prognosis and limited therapeutic solutions. Consequently, the present studies are committed to exploring potential biomarkers through bioinformatics analysis, which may serve as valuable prognostic predictors or novel therapeutic targets and provide new insights into the pathogenesis of GBM.

Methods: We filtered overlapping differentially expressed genes (DEGs) based on expression profilings from three GBM microarray datasets (GSE116520, GSE4290 and GSE68848) and combined RNA sequencing data from The Cancer Genome Atlas and the Genotype-Tissue Expression databases. Hub genes were prioritized from DEGs after performing protein-protein interaction (PPI) network analysis and weighted gene co-expression network analysis (WGCNA). This was followed by survival analysis to identify potential biomarkers among hub genes. Ultimately, the distributions of gene expressions, genetic alterations, upstream regulatory mechanisms and enrichments of gene functions of the identified biomarkers were analysed on public databases. QRT-PCR, immunohistochemical staining and western blotting was also used to confirm the gene expression patterns in GBM and normal brain tissues. CCK-8 assay clarified the effects of the genes on GBM cells.

Results: A total of 322 common DEGs were determined and nine genes were subsequently considered as hub genes by the combination of PPI network analysis and WGCNA. Only SLC12A5 had prognostic significance, which was deficient in GBM whereas especially enriched in normal neural tissues. SLC12A5 overexpression would inhibit cell proliferation of U251MG. Genetic alterations of SLC12A5 were rarely seen in GBM patients, and there was no apparent association existed between SLC12A5 expression and DNA methylation. SLC12A5 was prominently involved in ion transport, synapse and neurotransmitter.

Conclusion: SLC12A5 shows promise to function as a novel effective biomarker for GBM and deserves further systematic research.

Keywords: Bioinformatics analysis; Biomarker; Glioblastoma multiforme; KCC2; SLC12A5.

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