Integrated Single-cell and Spatial Transcriptomic Analysis Reveals YBX1 Drives Immune Regulation in GBM Progression

The RNA modification 5-methylcytosine (m5C) is widespread across various RNA types, significantly impacting RNA stability and translational efficiency. Accumulating evidence highlights its significant role within the tumorigenesis and progression of multiple malignancies. Nevertheless, the specific process through m5C is implicated in Glioblastoma (GBM) remains unclear. We conducted acomprehensive analysis of m5C expression distribution in single-cell GBM data. Our findings revealed elevated m5C scores in GBM single-cell data compared to the normal group. Additionally, multiple tumors exhibited significantly higher m5C scores than the normal group. Moreover, there was a positive correlation observed between the m5C score and inflammation score. m5C regulatory factor YBX1 exhibited a heightened expression in GBM, correlating closely with metastatic tendencies and an unfavorable prognosis across various cancer types. YBX1 has different biological functions in myeloid cells 1 and myeloid cells 2. YBX1 may act as immunosuppressive regulator by inhibiting the NF-κB pathway and inflammatory response in myeloid cells 1. YBX1 is essential for immune infiltrates, which creates a highly immunosuppressive tumor microenvironment by TNF signaling pathway in myeloid cells 2. YBX1+ neoplastic cells promote cell proliferation by NF-κB pathway. APOE mediates the interaction of YBX1+ myeloid cells and neoplastic cells by NF-κB.