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Abstract
Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients.
Highlights
Grades III and IV are designated as high-grade and are usually regarded as malignant
To identify the genes that are associated with the severity of glioma, we downloaded a high-throughput gene expression dataset from the Gene Expression Omnibus (GEO) database (GEO accession: GSE43289), which was based on the Affymetrix Human Genome U133 Plus 2.0 Array
We identified a prognostic gene signature composed of 18 ion channel genes, which successfully predicted glioma outcome in three independent validation cohorts
Summary
Grades III and IV are designated as high-grade and are usually regarded as malignant. Ion channels have been reported to be widely expressed in glia cells[16] and play a critical role in malignant glioma[17,18]. 16 of these 18 ion channel genes (89%) were down-regulated in high grade gliomas This signature successfully distinguishes glioma patients with high death-risk from the ones with low risk. This signature is independent of and improves on traditional prognostic factors in glioma. These results highlight the utility of ion channel genes as valuable biomarkers for glioma outcome prediction and for potentially facilitating individualized therapies in this disease
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