Systemic Proteomic Remodeling Following Nephrectomy in Renal Cell Carcinoma 2257687

Abstract Introduction Renal cell carcinoma (RCC) exerts widespread systemic effects that extend beyond the tumor microenvironment. However, how the removal of the primary tumor reshapes the circulating proteome remains largely undefined. Characterizing these changes may reveal biomarkers of immune recovery and mechanisms by which tumors disrupt systemic immune function. Methods We profiled plasma from 16 RCC patients collected before and after nephrectomy using the SomaLogic SOMAscan 11k assay v5.0, which quantifies 11,000 proteins. Data were z-score normalized and scaled in R. Differential abundance was analyzed using paired t-tests with false discovery rate (FDR) correction. Pathway analysis was performed using the GSEA package. Protein-protein correlation networks were constructed using the igraph package, and global topological parameters (node degree, edge strength, and network density) were compared before and after nephrectomy. Results Nephrectomy induced broad proteomic remodeling consistent with systemic homeostatic restoration. Differential abundance and pathway enrichment analysis identified 1,737 significantly altered proteins (FDR < 0.05), with decreases in pathways and mediators of immune suppression following tumor removal. Network analysis demonstrated a reduction in extremes in protein-protein correlations, node degree, and interaction strength, indicating a loss of tumor-driven network polarization. Together, these results suggest that the presence of RCC disrupts protein co-regulation, which normalizes following tumor removal. Conclusion Our findings demonstrate that RCC drives coordinated systemic proteomic dysregulation that is partially reversed after nephrectomy. The observed reduction in network extremes reflects a global rebalancing of circulating protein interactions, providing insight into how tumors perturb systemic physiology. Plasma proteomics and network metrics may offer sensitive indicators of systemic immune recovery and potential biomarkers of post-surgical immune restoration. Funding Source n/a Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)