Quantitative proteomic analysis of gastric cancer tissue reveals novel proteins in platelet-derived growth factor B signaling pathway

2017 
// Fang Liu 1, 2, * , Yuan Zhang 1, * , Tingting Men 1 , Xingyue Jiang 2 , Chunhua Yang 1 , He Li 4 , Xiaodan Wei 1 , Dong Yan 1 , Gangming Feng 5 , Jianke Yang 1 , Jonas Bergquist 3 , Bin Wang 2 , Wenguo Jiang 1 , Jia Mi 1, 3 , Geng Tian 1 1 Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong Province, 264003 China 2 Department of Radiology, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong Province, 256603 China 3 Department of Chemistry – BMC, Uppsala University, Uppsala, 75124, Sweden 4 Department of Gastric and Intestine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province, 264003 China 5 Yantai Institute, China Agriculture University, Yantai, Shandong Province, 264670 China * Shared first author Correspondence to: Geng Tian, email: Tiangeng@live.se Wenguo Jiang, email: jiangwg@foxmail.com Jia Mi, email: jia.mi@kemi.uu.se Keywords: proteomic, PDGF-B, gastric cancer, PRDX5, pathway Received: December 02, 2016      Accepted: February 07, 2017      Published: March 06, 2017 ABSTRACT Gastric cancer is one of the most common cancers in Asian countries. Searching for reliable biomarkers involving the development of gastric cancer is important for clinical practice. Quantitative proteomics has become an important method contributed to the discovery of novel diagnostic or therapeutic targets for the management of cancer. Here, we identified differently expressed proteins in gastric cancer and normal gastric tissues by using the high resolution mass spectrometer. Among the total of 2280 identified proteins, 87 were differentially expressed between gastric cancer and normal gastric tissues. Notably, several significant proteins are in the PDGF-B signaling pathway, including peroxiredoxin5 (PRDX5), S100A6, calreticulin (CALR) and cathepsin D (CTSD), which were validated by western blot. Furthermore, upstream regulators including PDGF-B, PDGFR-β, Akt, eIF4E and p70s6K were found significantly increased in the gastric cancer tissues. In addition, silencing of PRDX5 and PDGF-B suppressed the proliferation of gastric cancer cells in vitro . The administration of exogenous PDGF-BB recovered the reduced expression of PDGF-B signaling pathway in PDGF-B knockdown cells. Taken together, our findings suggested that PDGF-B signaling pathway plays an important role in the regulation of gastric cancer proliferation and the inhibition of this pathway may be a potential approach for treatment of gastric cancer.
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