Zhang Yushi, Cai Yi, Yu Hongyan, Li Hanzhong
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Biomed Res Int. 2015;2015:802153. doi: 10.1155/2015/802153. Epub 2015 Sep 3.
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), 0.760.96), 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.
肾细胞癌（RCC）是最致命的泌尿系统癌症之一，约80%的RCC为透明细胞型（ccRCC）。然而，目前尚无用于准确诊断RCC的血清生物标志物。在本研究中，我们使用相对和绝对定量的等压标签（iTRAQ）标记和液相色谱-串联质谱（LC-MS/MS）分析，对ccRCC患者和对照组的血清样本进行了定量蛋白质组学分析，以找出差异表达的蛋白质。总体而言，与对照组相比，早期ccRCC中有16种蛋白质显著上调（比值>1.5），14种蛋白质显著下调（比值<0.67）。选择了热休克蛋白71（HSC71），随后在六组独立的患者中通过蛋白质免疫印迹法进行了验证。酶联免疫吸附测定（ELISA）随后证实HSC71是一种潜在的血清生物标志物，可用于区分RCC与良性泌尿系统疾病，其操作特征曲线（ROC）下面积（AUC）为0.86（95%置信区间（CI），0.760.96），在阈值为15 ng/mL时，特异性为80%（95%CI 6192%），灵敏度为87%（95%CI 69%~96%）。基于iTRAQ的定量蛋白质组学分析导致血清HSC71被鉴定为RCC的一种新型血清生物标志物，对ccRCC的早期诊断特别有用。
