Spatial and Single-cell Multi-omics Approaches Unravel the Geneticand Immunological Landscape of SIRPB1 in Kidney Renal Clear CellCarcinoma

Introduction: Signal regulatory protein beta 1 (SIRPB1) is a member of the signal regulatory protein family and functions as a receptor-type glycoprotein. It participates in immune modulation through pathways connected with receptor tyrosine kinases. While its role in immunity has been reported, the relevance of SIRPB1 to the development and progression of kidney renal clear cell carcinoma (KIRC) has not been well established. Methods: We integrated multi-omics datasets, including TCGA KIRC (n ≈ 530) and GEO cohorts, to evaluate SIRPB1 expression, prognostic value, mutational associations, and immune infiltration patterns. Spatial transcriptomics and single-cell RNA sequencing were used to characterize the tumor microenvironment. Experimental validation was performed using immunohistochemistry and triple immunofluorescence on a tissue microarray containing 59 human renal tumor specimens. Pharmacogenomic profiling and drug response analyses were conducted using CRISPR-based perturbation data from RCC cell lines (predominantly ccRCC/KIRC-derived) Results: SIRPB1 expression was significantly elevated in advanced-stage tumors and correlated with poor overall survival. High SIRPB1 levels were associated with increased tumor grade, macrophage infiltration, and immune-related gene networks. Spatial and single-cell analyses identified macrophages as the dominant SIRPB1-expressing population within the tumor microenvironment. Loss of SIRPB1 sensitized RCC cell lines to several small-molecule compounds, revealing potential therapeutic vulnerabilities. Discussion: The data suggest that SIRPB1 not only reflects tumor aggressiveness but may also indicate responsiveness to therapeutic interventions. Its expression profile could therefore provide a basis for stratifying patients and optimizing treatment approache Conclusion: SIRPB1 emerges as a candidate biomarker with diagnostic, prognostic, and therapeutic relevance in KIRC. A patent application has been filed in relation to SIRPB1-based diagnostic and therapeutic strategies.