Influence of SLC40A1 on Cytokine Interactions and Immune Infiltration in Glioblastoma

• DOI: 10.1007/s12017-024-08789-y
• Publication Date: 2024-05-16T03:36:52Z
• Authors: Jiahao Jiang; Riquan Duan; Junle Zhu; Junqing Yan; Jingliang Ye; Chun Luo
• Keywords: Gene Expression Regulation, Neoplastic; Male; Brain Neoplasms; Tumor Microenvironment; Interleukin-18; Humans; Cytokines; Female; Middle Aged; Glioblastoma; Prognosis; Cation Transport Proteins; Aged

Abstract Numerous studies have explored the various functions of SLC40A1 in cancer development. However, the role of SLC40A1 in primary glioblastoma necessitates further investigation. Initially, we observed that GBM patients with high SLC40A1 expression had a more favorable prognosis compared to those with low expression levels, as evidenced by the analysis of the TIMER database. Subsequent analysis using the TCGA database enabled us to identify potential mechanisms. Further analyses, including GO, KEGG, GSEA, immune infiltration, and correlation analyses, revealed that SLC40A1 primarily affected cytokine interactions, particularly with CCL14 and IL18, resulting in changes in the immune microenvironment and ultimately leading to better prognosis in GBM patients. We validated our findings by examining a tissue microarray with 180 samples, confirming that GBM patients with high SLC40A1 protein expression exhibited more favorable prognostic outcomes compared to those with low expression levels. Immunofluorescence analysis also showed a significant correlation between SLC40A1 protein expression and the expression of IL18 and CCL14 proteins. These findings suggest that SLC40A1 may play a role in GBM pathogenesis by modulating the tumor immune microenvironment through the regulation of IL18 and CCL14. Hence, targeting SLC40A1 might offer potential benefits for immunotherapeutic interventions and prognostic assessments in GBM patients.