title: iTRAQ-Based Quantitative Proteomic Analysis Identified HSC71 as a Novel Serum Biomarker for Renal Cell Carcinoma.
abstract: 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.
authors.affiliation: Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Hanzhong
authors.initials: H
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D050883:HSC70 Heat-Shock Proteins / Q000097:blood*; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D007680:Kidney Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human