Elucidating the role of SLC4A7 in glioma prognosis: A comprehensive approach combining bioinformatics, single-cell analysis, and tissue validation

Abstract

Background: Gliomas, prevalent and lethal brain tumors, present limited treatment options despite advancements in understanding their molecular features. SLC4A7, an SLC4 family member and potential biomarker, is involved in acid-base regulation, affecting cancer cell growth. Targeting this mechanism may offer new therapeutic strategies. Aim: This study examines SLC4A7's role in gliomas and its potential as a therapeutic target. Methods: Genomic, whole exon sequencing, and single-cell sequencing datasets from glioma patients were processed and analyzed, followed by gene set enrichment analysis (GSEA). Cellular components and immune cell populations were investigated using 12-cell state and CIBERSORT analyses. Tissue microarray and immunohistochemistry were employed, with an automated semi-quantitative system scoring staining. ANOVA determined the significance of immunostaining scores related to clinical parameters. Results: Our data found increased SLC4A7 in tumor components correlated with higher tumor grading and poorer prognosis. Immunohistochemistry confirmed a relationship between SLC4A7 protein expression with tumor grade and the proliferation index. GSEA linked high SLC4A7 to cell proliferation and inflammation signaling. PIK3CAs were identified as a potential upstream in IDH mutant glioma but not in IDH wildtype. A positive correlation between heightened SLC4A7 expression and tumor mutation burden suggested genomic instability's role in SLC4A7 upregulation. Cellular heterogeneity analysis highlighted the importance of inflammatory cells, particularly macrophage M0. Conclusion: This study emphasizes SLC4A7's significance in adult gliomas, associating increased expression with high tumor grade, poor prognosis, enhanced proliferation, and inflammation. Investigating SLC4A7 may provide insights into cancer biology and contribute to developing innovative therapeutic targets for improved brain tumor treatments.

Keywords

• slc4a7
• glioblastoma
• the cancer genome atlas
• chinese glioma genome atlas
• gene set enrichment analysis
• tumor mutation burden
• microsatellite instability
• cibersort
• single-cell sequencing