Abstract
BackgroundGastrointestinal 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.MethodsFive 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.ResultsA 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.ConclusionsOur novel findings provide further understanding of acetylome in GIST and might demonstrate the possibility in the acetylation targeted diagnosis and therapy of GIST.
Highlights
Gastrointestinal stromal tumor (GIST) is a common digestive tract tumor with high rate of metastasis and recurrence
Acetylation is a key post‐modification in GISTs Western blot results showed that under the same conditions, the number of bands displayed by the pan-acetylated antibody was higher, and the acetylated bands were more obvious under the same exposure time compared with other modifications
Functional annotation of the Lys acetylome in GIST We further explored the regulatory effect of lysine acetylation on cellular function, Gene Ontology (GO) annotations were used which fell into three broad categories: Biological Process, Cellular Component, and Molecular Function
Summary
Gastrointestinal stromal tumor (GIST) is a common digestive tract tumor with high rate of metastasis and recurrence. We understand the genome, transcriptome and proteome in GIST. Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumors of the gastrointestinal tract and originate from interstitial cells of Cajal [1]. Until 1983, Mazur and Clark [3] used the name gastrointestinal stromal tumors, including all interstitial-derived tumors, as well as non-epithelial tumors of varying degrees of differentiation, such as leiomyoma and Schwannoma. GISTs mostly occur in the elderly, usually under the mucosa, and in other parts of the gastrointestinal tract and are common. Most GISTs have shown to bear c-kit proto-oncogene mutations, and express CD117 and CD34 [5, 6]. Relevant medical research in the United States of America shows that GISTs have an annual incidence of 11.0 to 19.6 individuals/1 million individuals [8, 9]
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