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High expression of N-type calcium channel indicates a favorable prognosis in gliomas.

ABSTRACT: For the diagnosis and prognosis of glioma, the development of prognostic biomarkers is critical. The N-type calcium channel, whose predominant subunit is encoded by calcium voltage-gated channel subunit alpha1 B (CACNA1B), is mostly found in the nervous system and is closely associated with neurosensory functions. However, the link between the expression of CACNA1B and glioma remains unknown. We used ONCOMINE to explore the differences in CACNA1B expression among different cancers. We then conducted survival analysis and COX analysis using TCGA_LGG and TCGA_GBM datasets, which were divided into CACNA1Bhigh and CACNA1Blow based on the median. We examined the differences in other favorable prognostic markers or clinical characteristics between CACNA1Bhigh and CACNA1Blow using t tests. Differentially expressed genes were identified, and KEGG pathway enrichment was performed. We compared the expression of methyltransferases and analyzed the differentially methylated regions. Immunohistochemistry results were retrieved from the Human Protein Atlas database for validation purposes. CACNA1B was expressed at lower levels in gliomas, and, for the first time, we found that high expression of CACNA1B in gliomas predicts a good prognosis. Other favorable prognostic markers, such as isocitrate dehydrogenase mutation, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase promoter methylation, were increased in tandem with high expression of CACNA1B. Differentially expressed genes were enriched in multiple pathways related to cancer progression and aberrant epigenetic alterations were significantly associated with CACNA1B. High expression of N-type calcium channels indicates a favorable prognosis for gliomas. This study provides a better understanding of the link between gliomas and N-type calcium channels and may offer guidance for the future treatment of gliomas.

SUBMITTER: Li G

PROVIDER: S-EPMC9239611 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose: Breast cancer is a highly heterogeneous malignancy, seriously threatening female health worldwide and inducing higher mortalities. Few have the studies evaluated Fms-like TyrosineKinase-3 (FLT3) in prognostic risk, immunotherapy or any other treatment of breast cancer. Our study focused on investigating the function of FLT3 in breast cancer. Patients and methods: Based on transcriptome and methylation data mined from The Cancer Gene Atlas (TCGA), we explored the clinical features of FLT3 expression in 1079 breast cancer samples. RT-qPCR in cell lines and tissue samples was used to verify the expression difference of FLT3. Kaplan–Meier survival analysis and cox regression models were employed for screening of FLT3 with potential prognostic capacity. Subsequently, functional analysis of the co-expressed genes was conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene-set enrichment analysis (GSEA). The correlation between FLT3 expression and tumor immune infiltration was jointly analyzed with estimate, ssGSEA, TIMER, and TISIDB. Then we employed checkpoint-related molecules, immunophenoscore (IPS), and tumor mutation burden (TMB) to assess the efficacy of immuno-checkpoint inhibitors (ICIs). Pearson correlation coefficient was employed to exam the association between DNA methylation and FLT3 expression. Results: FLT3 displays an elevated expression in breast cancer than normal pairs and is significantly associated with multiple clinical characteristics like age, menopause status, histological type, pathological stage, and molecular subtype as well as increased overall survival (OS). Additionally, FLT3 is a favorable independent prognostic factor. GO, KEGG, and GSEA suggested that FLT3 was associated with diversified immune-related features. FLT3 expression is correlated with the abundance of various immune cells namely CD4+T cell, CD8+ T cell, myeloid dendritic cell, and neutrophil as well as immune inhibitors especially CTLA4, which is positively correlated with FLT3 expression. Moreover, TMB displayed a negative correlation with FLT3 expression while IPS showed adverse tendency. Ultimately, the methylation of FLT3 downregulates the gene expression and closely binds to a few clinical parameters. Conclusion: FLT3 can be used for prognostic prediction and is relevant to immune infiltration in breast cancer. FLT3 may pave the way for future novel immunotherapies.

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High expression of N-type calcium channel indicates a favorable prognosis in gliomas.

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