Research Article iTRAQ-Based Quantitative Proteomic Analysis Identified HSC71 as a Novel Serum Biomarker for Renal Cell Carcinoma

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Renal cell carcinoma (RCC) is one of the most lethal urologic cancers and about 80 % of RCC are of the clear-cell type (ccRCC). However, there are no serum biomarkers for the accurate diagnosis of RCC. In this study, we performed a quantitative proteomic analysis on serum samples from ccRCC patients and control group by using isobaric tag for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to access differentially expressed proteins. Overall, 16 proteins were significantly upregulated (ratio> 1.5) and 14 proteins were significantly downregulated (ratio < 0.67) in early-stage ccRCC compared to control group. HSC71 was selected and subsequently validated by Western blot in six independent sets of patients. ELISA subsequently confirmed HSC71 as a potential serum biomarker for distinguishing RCC from benign urologic disease with an operating characteristic curve (ROC) area under the curve (AUC) of 0.86 (95 % confidence interval (CI), 0.76∼0.96), achieving sensitivity of 87 % (95 % CI 69%∼96%) at a specificity of 80 % (95 % CI 61∼92%) with a threshold of 15 ng/mL. iTRAQ-based quantitative proteomic analysis led to identification of serum HSC71 as a novel serum biomarker of RCC, particularly useful in early diagnosis of ccRCC. 1