Gastrointestinal stromal tumor (GIST) is a common digestive tract tumor with high rate of metastasis and recurrence. Currently, we understand the genome, transcriptome and proteome in GIST. However, posttranscriptional modification features in GIST remain unclear. In the present study, we aimed to construct a complete profile of acetylome in GIST. Five common protein modifications, including acetylation, succinylation, crotonylation, 2-hydroxyisobutyrylation, and malonylation were tested among GIST subgroups and significantly differentially- expressed lysine acetylation was found. The acetylated peptides labeled with Tandem Mass Tag (TMT)under high sensitive mass spectrometry, and some proteins with acetylation sites were identified. Subsequently, these proteins and peptides were classified into high/moderate (H/M) risk and low (L) risk groups according to the modified NIH classification standard. Furthermore, cell components, molecular function, biological processes, KEGG pathways and protein interaction networks were analyzed. A total of 2904 acetylation sites from 1319 proteins were identified, of which quantitative information of 2548 sites from 1169 proteins was obtained. Finally, the differentially-expressed lysine acetylation sites were assessed and we found that 42 acetylated sites of 38 proteins were upregulated in the H/M risk group compared with the L risk group, while 48 acetylated sites of 44 proteins were downregulated, of which Ki67 K1063Ac and FCHSD2 K24Ac were the two acetylated proteins that were most changed. Our novel findings provide further understanding of acetylome in GIST and might demonstrate the possibility in the acetylation targeted diagnosis and therapy of GIST.

中文翻译：

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胃肠道间质瘤中异常表达的赖氨酸乙酰化的定量蛋白质组学分析

胃肠道间质瘤（GIST）是一种常见的消化道肿瘤，具有很高的转移和复发率。目前，我们了解GIST中的基因组，转录组和蛋白质组。但是，GIST中的转录后修饰功能仍不清楚。在本研究中，我们旨在在GIST中构建一个完整的乙酰酶组图谱。在GIST亚组中测试了5种常见的蛋白质修饰，包括乙酰化，琥珀酰化，巴豆酰化，2-羟基异丁酰化和丙二酰化，发现了差异显着表达的赖氨酸乙酰化。在高灵敏度质谱分析下，用串联质谱标签（TMT）标记的乙酰化肽被鉴定出来，并且鉴定出一些具有乙酰化位点的蛋白质。随后，根据修订的NIH分类标准，将这些蛋白质和多肽分为高/中（H / M）风险和低（L）风险组。此外，分析了细胞成分，分子功能，生物学过程，KEGG途径和蛋白质相互作用网络。鉴定出来自1319个蛋白质的2904个乙酰化位点，其中获得了来自1169个蛋白质的2548个位点的定量信息。最后，评估了差异表达的赖氨酸乙酰化位点，我们发现与L风险组相比，H / M风险组中38个蛋白的42个乙酰化位点被上调，而44个蛋白中的48个乙酰化位点被下调，其中Ki67 K1063Ac和FCHSD2 K24Ac是变化最大的两个乙酰化蛋白质。