期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 500, 期 2, 页码 411-417出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.04.089
关键词
SPG20; Methylation; Gastric cancer; Proliferation; Prognosis
资金
- National Natural Science Foundation of China [81502442]
Spastic paraplegia 20 methylation was characterized in gastric cancer in our previous study. However, its mechanism remains unknown. Cell proliferation, colony formation, flow cytometry, wound healing, in vitro Transwell assays and in vivo xenografts were performed. A nomogram model was established to make a more accurate prognostic prediction for gastric cancer patients. Knockout of Spastic paraplegia 20 promoted gastric cancer cell proliferation, G2/M arrest in vitro and tumor growth in vivo. The EGFR/MAPK pathway was activated as a consequence of Spastic paraplegia 20 deletion. EGFR kinase or ERK1/2 inhibitors impaired Spastic paraplegia 20 knockout-induced cancer cell growth. Gastric cancer patients with poor spartin expression (72/161, 44.7%) exhibited a worse prognosis compared with the high expression group with median survival times of 16 and 54 months, respectively. The nomogram model stratified gastric cancer patients into 3 distinct prognostic groups with 3-year survival rates of 100%, 77%, and 35%. Furthermore, it had a better discrimination than the TNM staging system (C index: 0.785, AIC: 752.8708 VS. C index: 0.712; AIC: 775.1223). Methylation-induced Spastic paraplegia 20 silencing facilitates gastric cancer cell proliferation by activating the EGFR/MAPK signaling pathway. The nomogram based on spartin expression provided significantly better discrimination compared with the traditional AJCC TNM staging system and provided an individualized prediction of the survival for gastric cancer patient survival. (C) 2018 Elsevier Inc. All rights reserved.
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