Prognostic Significance of CACNA1A in Glioma: An Integrated Bioinformatics and Experimental Analysis
Chengkai Yang, Minhao Huang, Kaizhang Liu, Junjie Yang, Chunhui HuaObjective
This study aims to determine the prognostic significance of CACNA1A in glioma by examining its expression and functional involvement in the disease.
Methods
We compiled RNA‐seq and clinical data obtained from the following databases: the Chinese Glioma Genome Atlas (CGGA) database, the Genotype‐Tissue Expression (GTEx) database, and The Cancer Genome Atlas (TCGA) database. We conducted various bioinformatics studies, including differential gene expression, Kaplan–Meier (KM) survival curve, univariate regression, nomogram, receiver operating characteristic (ROC) curve, gene function enrichment, and immune cell infiltration analyses. We investigated the potential connection between CACNA1A and immune infiltration and checkpoints. We implemented qRT‐PCR and Western blotting to confirm whether CACNA1A is expressed in glioma cells and tissues. Transwell experiments were conducted to determine the association between CACNA1A expression and glioma cell invasion and migration.
Results
CACNA1A transcript levels were significantly downregulated across multiple cancer types. We observed a significant downregulation of CACNA1A in gliomas relative to normal brain tissues. The CACNA1A expression was strongly associated with many clinicopathologic variables, including age, 1p19q codeletion status, World Health Organization (WHO) grade, isocitrate dehydrogenase (IDH) mutant status, and histological subtype. Low CACNA1A expression predicted unfavorable survival based on KM survival curves, Cox regression analysis, and the nomogram model. In addition, a comparison between the high‐ and low‐CACNA1A expression groups revealed substantial enrichment of the cytokine–cytokine receptor interaction, neuroactive ligand–receptor interaction, calcium signaling, and cAMP signaling pathways. According to the immune infiltration analysis, lower immune checkpoint concentrations, immune scores, and immunocyte proportions were all associated with the elevated CACNA1A expression. These findings were consistent with the anticipated outcomes of the bioinformatics analysis.
Conclusions
Our research shows that CACNA1A expression holds prognostic significance in glioma. Glioma patients with CACNA1A overexpression had more favorable prognoses. These findings may serve as a starting point for future investigations into glioma, P/Q‐type calcium channels, and their interactions.