Quantitative proteomics by SWATH-MS reveals sophisticated metabolic reprogramming in hepatocellular carcinoma tissues.
Quantitative proteomics by SWATH-MS reveals sophisticated metabolic reprogramming in hepatocellular carcinoma tissues.
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SWATH-MS 定量蛋白质组学揭示肝细胞癌组织中复杂的代谢重编程
DOI：
10.1038/srep45913
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发表时间：
2017-04-05
影响因子：
4.6
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Gao Y;Wang X;Sang Z;Li Z;Liu F;Mao J;Yan D;Zhao Y;Wang H;Li P;Ying X;Zhang X;He K;Wang H
肝细胞癌（HCC）是世界上最常见的癌症之一，了解其分子发病机制是管理这种疾病的关键。全理论质谱连续窗口采集（SWATH-MS）是寻找参与HCC发生和进展的关键蛋白质的最佳蛋白质组学策略。在这项研究中，使用SWATH-MS策略进行了肿瘤和邻近非肿瘤肝组织的定量蛋白质组学研究。总共有4，216种蛋白质被可靠地定量，338种蛋白质差异表达，与邻近的非肿瘤组织相比，HCC组织中有191种蛋白质上调，147种蛋白质下调。功能分析揭示了不同的途径富集的上调和下调的蛋白质。最显著下调的蛋白质参与代谢途径。值得注意的是，我们的研究揭示了HCC中复杂的代谢重编程，包括磷酸戊糖途径的改变;丝氨酸、甘氨酸和肌氨酸的生物合成/代谢;糖酵解;脂肪酸生物合成;和脂肪酸β-氧化。27种代谢酶，包括PCK 2，PDH和G6 PD，在这项研究中，显着变化。据我们所知，这项研究提供了HCC中组织特异性代谢重编程的最完整视图，确定了数百种差异表达的蛋白质，这些蛋白质共同构成了新药物靶点或诊断生物标志物发现的丰富资源。
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and understanding its molecular pathogenesis is pivotal to managing this disease. Sequential window acquisition of all theoretical mass spectra (SWATH-MS) is an optimal proteomic strategy to seek crucial proteins involved in HCC development and progression. In this study, a quantitative proteomic study of tumour and adjacent non-tumour liver tissues was performed using a SWATH-MS strategy. In total, 4,216 proteins were reliably quantified, and 338 were differentially expressed, with 191 proteins up-regulated and 147 down-regulated in HCC tissues compared with adjacent non-tumourous tissues. Functional analysis revealed distinct pathway enrichment of up- and down-regulated proteins. The most significantly down-regulated proteins were involved in metabolic pathways. Notably, our study revealed sophisticated metabolic reprogramming in HCC, including alteration of the pentose phosphate pathway; serine, glycine and sarcosine biosynthesis/metabolism; glycolysis; gluconeogenesis; fatty acid biosynthesis; and fatty acid β-oxidation. Twenty-seven metabolic enzymes, including PCK2, PDH and G6PD, were significantly changed in this study. To our knowledge, this study presents the most complete view of tissue-specific metabolic reprogramming in HCC, identifying hundreds of differentially expressed proteins, which together form a rich resource for novel drug targets or diagnostic biomarker discovery.