MS4A6A is a new prognostic biomarker produced by macrophages in glioma patients

Abstract

MS4A6A has been recognized as being associated with aging and the onset of neurodegenerative disease. However, the mechanisms of MS4A6A in glioma biology and prognosis are ill-defined. Here, we show that MS4A6A is upregulated in glioma tissues, resulting in unfavorable clinical outcomes and poor responses to adjuvant chemotherapy. Multivariate Cox regression analysis suggested that MS4A6A expression can act as a strong and independent predictor for glioma outcomes (CGGA1: HR: 1.765, p < 0.001; CGGA2: HR: 2.626, p < 0.001; TCGA: HR: 1.415, p < 0.001; Rembrandt: HR: 1.809, p < 0.001; Gravendeel: HR: 1.613, p < 0.001). A protein–protein interaction (PPI) network revealed that MS4A6A might be coexpressed with CD68, CD163, and macrophage-specific signatures. Enrichment analysis showed the innate immune response and inflammatory response to be markedly enriched in the high MS4A6A expression group. Additionally, single-cell RNA sequencing (scRNA-seq) analysis revealed distinctive expression features for MS4A6A in macrophages in the glioma immune microenvironment (GIME). Immunofluorescence staining confirmed colocalization of CD68/MS4A6A and CD163/MS4A6A in macrophages. Correlation analysis revealed that MS4A6A expression is positively related to the tumor mutation burden (TMB) of glioma, displaying the high potential of applying MS4A6A to evaluate responsiveness to immunotherapy. Altogether, our research indicates that MS4A6A upregulation may be used as a promising and effective indicator for adjuvant therapy and prognosis assessment.