Quantitative Proteomics Identifies Secreted Diagnostic Biomarkers as well as Tumor-Dependent Prognostic Targets for Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the third most common and most malignant urological cancer, with a 5-year survival rate of 10% for patients with advanced tumors. Here, we identified 10,160 unique proteins by in-depth quantitative proteomics, of which 955 proteins were significantly regulated between tumor and normal adjacent tissues. We verified four putatively secreted biomarker candidates, namely, PLOD2, FERMT3, SPARC, and SIRPα, as highly expressed proteins that are not affected by intratumor and intertumor heterogeneity. Moreover, SPARC displayed a significant increase in urine samples of patients with ccRCC, making it a promising marker for the detection of the disease in body fluids. Furthermore, based on molecular expression profiles, we propose a biomarker panel for the robust classification of ccRCC tumors into two main clusters, which significantly differed in patient outcome with an almost three times higher risk of death for cluster 1 tumors compared with cluster 2 tumors. Moreover, among the most significant clustering proteins, 13 were targets of repurposed inhibitory FDA-approved drugs. Our rigorous proteomics approach identified promising diagnostic and tumor-discriminative biomarker candidates which can serve as therapeutic targets for the treatment of ccRCC. IMPLICATIONS: Our in-depth quantitative proteomics analysis of ccRCC tissues identifies the putatively secreted protein SPARC as a promising urine biomarker and reveals two molecular tumor phenotypes.

The role of sodium intake in nephrolithiasis: epidemiology, pathogenesis, and future directions.

The prevalence of nephrolithiasis has doubled over the last decade and the incidence in females now approaches that of males. Since dietary salt is lithogenic, a purported mechanism common to both genders is excess dietary sodium intake vis-a-vis processed and fast foods. Nephrolithiasis has far-reaching societal implications such as impact on gross domestic product due to days lost from work (stone disease commonly affects working adults), population-wide carcinogenic diagnostic and interventional radiation exposure (kidney stone disease is typically imaged with computed tomographic imaging and treated under imaging guidance and follow-up), and rising healthcare costs (surgical treatment will be indicated for a number of these patients). Therefore, primary prevention of kidney stone disease via dietary intervention is a low-cost public health initiative with massive societal implications. This primer aims to establish baseline epidemiologic and pathophysiologic principles to guide clinicians in sodium-directed primary prevention of kidney stone disease.