Immunological and Prognostic Role of Cell Differentiation Trajectory Defined Gene Signature in Glioma

Abstract

Glioma was characterized by its severe cellular heterogeneity during cell differentiation. Based on scRNA-seq and high throughput sequencing data, this research revealed the potential connections between cell differentiation trajectory and immune landscape in glioma. Glioma differentiation-related genes (GDRGs) were extracted from cell differentiation trajectories to establish a three-subtype molecular classification. Enrichment analysis indicated that GDRGs were involved in cell differentiation, intercellular adhesion, cytotoxicity, and cell cycle. ESTIMATE and CIBERSORT analysis showed that GDRGs and macrophages-related immune checkpoints (CD163, CD206, LILRB4, LILRB2, LILRB1, CD47, and SIRPα) promoted M2-dominated immune landscape in glioma. Finally, a novel prognostic risk score (RS) signature and nomogram based on 8 GDRGs (SOX4, MEX3A, EGFR, NES, ENC1, NEFL, NNAT, and TMSB15A) were established to predict the patient's 3-years and 5-years OS In conclusion, the molecular subtypes defined by cell differentiation trajectories predicted the M2-dominated immune landscape. GDRGs named SOX4, MEX3A, EGFR, NES, ENC1, NEFL, NNAT, and TMSB15A could be regarded as novel prognostic signatures and potential targets for immunotherapy.