Systematic Comparative Protein Expression Profiling of Clear Cell Renal Cell Carcinoma

Abstract

Proteome-based technologies represent powerful tools for the analysis of protein expression profiles, including the identification of potential cancer candidate biomarkers. Thus, here we provide a comprehensive protein expression map for clear cell renal cell carcinoma established by sys- tematic comparative two-dimensional gel electrophoresis- based protein expression profiling of 16 paired tissue sys- tems comprising clear cell renal cell carcinoma lesions and corresponding tumor-adjacent renal epithelium using over- lapping narrow pH gradients. This approach led to the map- ping of 348 distinct spots corresponding to 248 different protein identities. By implementing restriction criteria con- cerning their detection frequency and overall regulation mode, 28 up- and 56 down-regulated single target spots were considered as potential candidate biomarkers. Based on their gene ontology information, these differentially ex- pressed proteins were classified into distinct functional groups and according to their cellular distribution. More- over, three representative members of this group, namely calbindin, gelsolin, and heart fatty acid-binding protein, were selected, and their expression pattern was analyzed by immunohistochemistry using tissue microarrays. Thus, this pilot study provides a significant update of the current renal cell carcinoma map and defines a number of differ- entially expressed proteins, but both their potential as candidate biomarkers and clinical relevance has to be further explored in tissues and for body fluids like serum and urine. Molecular