Seliger Barbara, Dressler Sven P, Lichtenfels Rudolf, Kellner Roland
Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Proteomics. 2007 Dec;7(24):4601-12. doi: 10.1002/pmic.200700415.
Although the human genome has been decoded, the knowledge about the pathogenesis of diseases including cancer is still limited. By focusing on renal cell carcinoma (RCC) we here summarize the data of various research groups analyzing the protein/peptide expression profiles of tumor lesions/cell lines or serum obtained from patients and respective controls. Different powerful approaches such as 2-DE, PROTEOMEX/SERPA/SPEARS, and T cell epitope discovery upon elution of MHC class I-bound peptides in combination with MS/LC-MS/MS revealed 500 differentially expressed proteins. The overlap in target recognition limits the pool to 299 unique protein identities, but only few thereof (12%) have been validated. The management, analysis, and interpretation of the distinct data sets derived from 27 publications required bioinformatic restructuring of the results. However, the comprehensive analysis of the results expands the knowledge about the pathophysiology of RCC in particular of the most prominent clear cell subtype by providing information on the differentially expressed proteins, their regulation status in RCC compared to normal kidney epithelium next to additional information on MHC-presented T cell epitopes and on serological targets. Despite the low number of validated differentially expressed proteins some of them might serve as candidate biomarkers for the diagnosis and/or as therapeutic targets.
尽管人类基因组已被解码,但对于包括癌症在内的疾病发病机制的了解仍然有限。我们聚焦于肾细胞癌(RCC),在此总结了各个研究小组分析从患者及相应对照获取的肿瘤病变/细胞系或血清的蛋白质/肽表达谱的数据。不同的强大方法,如二维电泳(2-DE)、蛋白质组学扩展技术/血清蛋白质组分析/肽段富集与质谱鉴定系统(PROTEOMEX/SERPA/SPEARS),以及在洗脱与MHC I类结合肽后结合质谱/液相色谱-串联质谱(MS/LC-MS/MS)的T细胞表位发现,揭示了500种差异表达的蛋白质。目标识别中的重叠将范围限制为299个独特的蛋白质身份,但其中仅有少数(12%)已得到验证。对来自27篇出版物的不同数据集的管理、分析和解读需要对结果进行生物信息学重组。然而,对结果的综合分析通过提供关于差异表达蛋白质的信息、它们在RCC中相对于正常肾上皮的调控状态,以及关于MHC呈递的T细胞表位和血清学靶点的额外信息,扩展了对RCC尤其是最常见的透明细胞亚型病理生理学的认识。尽管经过验证的差异表达蛋白质数量较少,但其中一些可能作为诊断的候选生物标志物和/或治疗靶点。