Urinary proteome and metabolome uncover tumor microenvironment and cellular metabolism changes of renal clear cell carcinoma

ABSTRACT: We applied LC-MS to profile the urine proteome and metabolome of 314 ccRCC, 341 healthy control and 49 kidney benign disease enrolled from three cohorts to a great depth. Functionally, we revealed significant changes of extracellular matrix (ECM) organization, complement and coagulation cascades, amino acid metabolism and fatty acid metabolism in ccRCC. Further cell origin annotation of cancer associated proteins revealed the potential role of myofibroblast cell, pericyte cell, vascular associated smooth muscle cell, and endothelial cell during ECM organization. Protein-protein correlation analysis suggested potential cell-cell communications in tumor TME, especially for tumor and myofibroblast cell. Finally, we discovered four potential urinary biomarkers, FGB,CILP, ITIH1, and GUCA2B, and established a model for ccRCC diagnosis with the AUC value of 0.84 in an external cohort. The model also showed discriminatory ability for ccRCC and benign with the AUC value of 0.75. Present study provided urinary molecular changes, which could reflect TME disorder and cellular metabolism reprogramming

ORGANISM(S): Homo Sapiens

SUBMITTER: Wei Sun  

PROVIDER: PXD064183 | iProX | Thu May 22 00:00:00 BST 2025

REPOSITORIES: iProX