Global PROTOMAP Profiling to Search for Biomarkers of Early-Recurrent Hepatocellular Carcinoma
Global PROTOMAP Profiling to Search for Biomarkers of Early-Recurrent Hepatocellular Carcinoma
复制标题
DOI：
10.1021/pr500262p
复制
发表时间：
2014-11-01
影响因子：
4.4
通讯作者：
Kondo, Tadashi
中科院分区：
文献类型：
--
作者：
Taoka, Masato;Morofuji, Noriaki;Kondo, Tadashi
本研究使用全局蛋白表达谱来寻找预测早期复发性肝细胞癌（HCC）的生物标志物。将手术切除的HCC组织与邻近的非肿瘤组织和正常肝组织进行比较，这些HCC组织来自手术后2年内复发或未复发的患者（早期复发）。我们使用PROTOMAP策略进行比较分析，该策略整合了变性聚丙烯酰胺凝胶电泳迁移率和基于高分辨率、半定量质谱的凝胶内消化胰蛋白酶肽鉴定。PROTOMAP允许检查复杂组织样品中蛋白质的大小、形貌和丰度的全局变化。这种方法确定了8438独特的蛋白质从45 708非冗余肽，并产生了蛋白质组范围内的表达和蛋白水解事件的变化可能引起的内在凋亡/坏死途径的地图。在早期复发的HCC组织中，87个蛋白质相对于其他组织差异表达（>= 20倍），其中46个蛋白质上调或特异性蛋白水解，其中41个蛋白质下调。该数据集包括属于各种功能类别的蛋白质，包括信号转导和细胞组织，特别是负责肝功能的主要催化途径，如尿素循环和解毒代谢。我们发现，异常蛋白水解似乎经常发生在肝癌复发的几个关键信号转导，包括STAT 1和δ-连环蛋白。对这些蛋白质的进一步研究将有助于开发新的临床应用。
This study used global protein expression profiling to search for biomarkers to predict early recurrent hepatocellular carcinoma (HCC). HCC tissues surgically resected from patients with or without recurrence within 2 years (early recurrent) after surgery were compared with adjacent nontumor tissue and with normal liver tissue. We used the PROTOMAP strategy for comparative profiling, which integrates denaturing polyacrylamide gel electrophoresis migratory rates and high-resolution, semiquantitative mass-spectrometry-based identification of in-gel-digested tryptic peptides. PROTOMAP allows examination of global changes in the size, topography, and abundance of proteins in complex tissue samples. This approach identified 8438 unique proteins from 45 708 nonredundant peptides and generated a proteome-wide map of changes in expression and proteolytic events potentially induced by intrinsic apoptotic/necrotic pathways. In the early recurrent HCC tissue, 87 proteins were differentially expressed (>= 20-fold) relative to the other tissues, 46 of which were up-regulated or specifically proteolyzed and 41 of which were down-regulated. This data set consisted of proteins that fell into various functional categories, including signal transduction and cell organization and, notably, the major catalytic pathways responsible for liver function, such as the urea cycle and detoxification metabolism. We found that aberrant proteolysis appeared to occur frequently during recurrence of HCC in several key signal transducers, including STAT1 and delta-catenin. Further investigation of these proteins will facilitate the development of novel clinical applications.