Panel of Candidate Biomarkers for Renal Cell Carcinoma
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- 作者：Dong Su Kim ; Yoon Pyo Choi ; Suki Kang ; Ming Qing Gao ; Baekil Kim ; Haeng Ran Park ; Young Deuk Choi ; Jong Baek Lim ; Hyung Jin Na ; Hye Kyung Kim ; Young-Pyo Nam ; Mi Hyang Moon ; Hae Ree Yun ; Dong Hee Lee
- 刊名：Journal of Proteome Research
- 出版年：2010
- 出版时间：July 2, 2010
- 年：2010
- 卷：9
- 期：7
- 页码：3710-3719
- 全文大小：443K
- 年卷期：v.9,no.7(July 2, 2010)
- ISSN：1535-3907
文摘
The timely diagnosis and therapeutic monitoring of human renal cell carcinoma (RCC) is limited by the lack of specific biomarkers. To identify candidate RCC biomarkers, we used 2-DE gel electrophoresis with mass spectrometry and 2-DE spot intensity-based ROC analysis to analyze 18 sets of paired normal and RCC tumor tissue including conventional, papillary, and chromophobe subtypes. Validation was performed with RCC patient plasma samples and confirmed by clustergram, shRNA, and immunohistochemistry assays. Cardinal candidates were evaluated by ELISA. The leading candidate biomarker that was upregulated in RCC samples according to the clustergram and validation analysis was nicotinamide N-methyltransferase (NNMT) (13/15, P < 0.0001). Other upregulated candidate biomarkers that were identified by this method include ferritin, hNSE, NM23, secretagogin, and l-plastin. The upregulation of NNMT in RCC was confirmed by immunoblotting and immunohistochemistry. Analysis of fractionated membrane-associated proteins identified CAP-G, mitofillin, tubulin α, RBBP7, and HSP27. Of these, RBBP7 and HSP27 were highly expressed in the chromophobe subtype of RCC (3/3) but were absent from conventional RCC (0/3). The triple combination of the NNMT, FTL, and hNSE biomarkers had the highest predictive capacity of 0.993, while NNMT was the single, most powerful candidate diagnostic biomarker for all types of RCC.