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Published on: October 20, 2016
MS4A6A is a new prognostic biomarker produced by macrophages in glioma patients
Chunyu Zhang1,2, Haitao Liu3, Yinqiu Tan4
1Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
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.
Insights
MS4A6A is elevated in glioma, predicting poor outcomes and response to chemotherapy. Its association with immune cells suggests potential for immunotherapy and prognosis assessment in brain tumors.
Area of Science:
- Neuro-oncology
- Cancer immunology
- Molecular diagnostics
Background:
- The role of MS4A6A in glioma pathogenesis and its clinical implications remain unclear.
- MS4A6A is implicated in aging and neurodegenerative diseases, suggesting a potential link to brain tumor development.
Purpose of the Study:
- To investigate the expression, prognostic value, and biological mechanisms of MS4A6A in glioma.
- To explore the association of MS4A6A with the glioma immune microenvironment and its potential as a predictive biomarker.
Main Methods:
- Analysis of MS4A6A expression in glioma tissues using multiple datasets (CGGA, TCGA, Rembrandt, Gravendeel).
- Multivariate Cox regression for prognostic value assessment.
- Protein-protein interaction network analysis, enrichment analysis, single-cell RNA sequencing (scRNA-seq), and immunofluorescence staining.
- Correlation analysis with tumor mutation burden (TMB).
Main Results:
- MS4A6A is upregulated in glioma, correlating with unfavorable clinical outcomes and poor response to adjuvant chemotherapy.
- MS4A6A expression is an independent predictor of glioma prognosis across multiple cohorts.
- MS4A6A is coexpressed with macrophage markers (CD68, CD163) and associated with innate immune and inflammatory responses.
- scRNA-seq confirms MS4A6A expression in glioma-infiltrating macrophages.
- MS4A6A expression positively correlates with TMB, indicating potential for immunotherapy response prediction.
Conclusions:
- Upregulated MS4A6A serves as a significant prognostic biomarker for glioma patients.
- MS4A6A's role in the glioma immune microenvironment highlights its potential utility in predicting response to adjuvant therapy and immunotherapy.
- MS4A6A is a promising indicator for assessing glioma prognosis and guiding treatment strategies.
