Does the Urinary Proteome Reflect ccRCC Stage and Grade Progression?

Abstract

Due its ability to provide a global snapshot of kidney physiology, urine has emerged as a highly promising, non-invasive source in the search for new molecular indicators of disease diagnosis, prognosis, and surveillance. In particular, proteomics represents an ideal strategy for the identification of urinary protein markers; thus, a urinomic approach could also represent a powerful tool in the investigation of the most common kidney cancer, which is clear cell Renal Cell Carcinoma (ccRCC). Currently, these tumors are classified after surgical removal using the TNM and nuclear grading systems and prognosis is usually predicted based upon staging. However, the aggressiveness and clinical outcomes of ccRCC remain heterogeneous within each stratified group, highlighting the need for novel molecular indicators that can predict the progression of these tumors. In our study, we explored the association between the urinary proteome and the ccRCC staging and grading classification. The urine proteome of 44 ccRCC patients with lesions of varying severity was analyzed via label-free proteomics. MS data revealed several proteins with altered abundance according to clinicopathological stratification. Specifically, we determined a panel of dysregulated proteins strictly related to stage and grade, suggesting the potential utility of MS-based urinomics as a complementary tool in the staging process of ccRCC.