Background: 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.
Methods: 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.
Results: 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.
Conclusions: Our novel findings provide further understanding of acetylome in GIST and might demonstrate the possibility in the acetylation targeted diagnosis and therapy of GIST.
Keywords: Acetylation; Gastrointestinal stromal tumor; PTM; Proteomics.