Jones Elizabeth Ellen, Powers Thomas W, Neely Benjamin A, Cazares Lisa H, Troyer Dean A, Parker Alexander S, Drake Richard R
Department of Cell and Molecular Pharmacology, MUSC Proteomics Center, Medical University of South Carolina, Charleston, SC, USA.
Proteomics. 2014 Apr;14(7-8):924-35. doi: 10.1002/pmic.201300434. Epub 2014 Mar 3.
Reducing the incidence and mortality rates for clear cell renal cell carcinoma (ccRCC) remains a significant clinical challenge with poor 5-year survival rates. A unique tissue cohort was assembled of matched ccRCC and distal nontumor tissues (n = 20) associated with moderate risk of disease progression, half of these from individuals who progressed to metastatic disease and the other half who remained disease free. These tissues were used for MALDI imaging MS profiling of proteins in the 2-20 kDa range, resulting in a panel of 108 proteins that had potential disease-specific expression patterns. Protein lysates from the same tissues were analyzed by MS/MS, resulting in identification of 56 proteins of less than 20 kDa molecular weight. The same tissues were also used for global lipid profiling analysis by MALDI-FT-ICR MS. From the cumulative protein and lipid expression profile data, a refined panel of 26 proteins and 39 lipid species was identified that could either distinguish tumor from nontumor tissues, or tissues from recurrent disease progressors from nonrecurrent disease individuals. This approach has the potential to not only improve prognostic assessment and enhance postoperative surveillance, but also to inform on the underlying biology of ccRCC progression.
降低透明细胞肾细胞癌(ccRCC)的发病率和死亡率仍然是一项重大的临床挑战,其5年生存率较低。我们组建了一个独特的组织队列,包含匹配的ccRCC和远端非肿瘤组织(n = 20),这些组织具有中等疾病进展风险,其中一半来自进展为转移性疾病的个体,另一半则无疾病进展。这些组织用于对2 - 20 kDa范围内的蛋白质进行基质辅助激光解吸电离成像质谱分析(MALDI成像MS分析),得到一组具有潜在疾病特异性表达模式的108种蛋白质。对相同组织的蛋白质裂解物进行串联质谱分析(MS/MS),鉴定出56种分子量小于20 kDa的蛋白质。相同组织还用于通过基质辅助激光解吸电离傅里叶变换离子回旋共振质谱(MALDI-FT-ICR MS)进行全局脂质谱分析。从累积的蛋白质和脂质表达谱数据中,鉴定出一组经过优化的26种蛋白质和39种脂质种类,它们能够区分肿瘤组织与非肿瘤组织,或者区分疾病复发进展者的组织与无疾病复发个体的组织。这种方法不仅有可能改善预后评估并加强术后监测,还能为ccRCC进展的潜在生物学机制提供信息。