Comparative proteomic analysis of kit-positive gastrointestinal stromal tumors based on differential risk classification

Abstract

Objective To screen new molecular markers related to invasion and metastasis of gastrointestinal stromal tumors (GISTs) by analyzing differential protein expression profiles between high-risk and low-risk GISTs with c-kit mutation. Methods Two dimensional polyacrylamide gel electrophoresis (2D-PAGE) was used to detect the differentially expressed proteins in 5 cases of high-risk and 5 cases of low-risk GIST tissues with c-kit mutation respectively, and the differentially expressed protein markers were analyzed and identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Results By comparative analysis of protein expression profiles we found 41 differentially expressed protein spots. Using MALDI-TOF-MS technique for mass spectrometry analysis of differentially expressed protein spots we successfully identified 27 different protein molecules. Of these, 14 proteins including aldehyde dehydrogenase 1 family, member A2 (ALDH1A2), ubiquinol cytochrome c reductase core protein 1 (UQCRC1), chaperonin containing TCP1 subunit 2 (CCT-2), pyruvate dehydrogenase beta (PDHB), peroxiredoxin 3 (PRDX3), protease activator 28 beta (Pa28β), cytochrome c oxidase subunit 5A (COX5A), caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP), Tu translation elongation factor, mitochondrial (TuFM), glutathione S-transferase omega 1 (GSTO1), hypocretin receptor 1 (HCRTR1), NM23-H1 and an unknown protein were upregulated in high-risk GISTs. 13 proteins included apolipoprotein A1 (APOA1), heme binding protein 1 (HEBP1), chromosome 1 open reading frame 123 (C1orf123), heat shock protein beta-6 (HSPB6), SH3 domain-binding glutamic acid-rich-like protein (SH3BGRL), glutathione S-transferase Mu 2 (GSTM2), tropomyosin alpha-1 chain (TPM1), protein disulfide-isomerase A3 (PDIA3), dimethylarginine dimethylaminohydrolase 1 (DDAH1), tetratricopeptide repeat domain 1 (TTC1), heterogeneous nuclear ribonucleoprotein C (HNRNPC) and DJ-1 were downregulated in high-risk GISTs. Conclusion The 27 differentially expressed proteins had the potential to be the specific tumor biomarkers for predicting the prognosis and warning of the metastasis of GISTs. Key words: Gastrointestinal stromal tumors; Proteomics; Molecular markers; Neoplasm metastasis