Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 227W, Yanta Road, Xi'an, Shaanxi, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, 227W, Yanta Road, Xi'an, Shaanxi, China.
Biochem Biophys Res Commun. 2018 Jun 2;500(2):411-417. doi: 10.1016/j.bbrc.2018.04.089. Epub 2018 Apr 18.
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.
在我们之前的研究中，发现痉挛性截瘫 20 甲基化存在于胃癌中。然而，其机制尚不清楚。进行了细胞增殖、集落形成、流式细胞术、划痕愈合、体外 Transwell 测定和体内异种移植实验。建立了列线图模型，以便更准确地预测胃癌患者的预后。敲除痉挛性截瘫 20 促进胃癌细胞体外增殖、G2/M 期阻滞和体内肿瘤生长。由于 Spastic paraplegia 20 的缺失，激活了 EGFR/MAPK 通路。EGFR 激酶或 ERK1/2 抑制剂削弱了 Spastic paraplegia 20 缺失诱导的癌细胞生长。与高表达组相比，72/161（44.7%）的胃癌患者 spartin 表达水平较差，其中位生存时间分别为 16 个月和 54 个月，预后较差。列线图模型将胃癌患者分为 3 个不同的预后组，3 年生存率分别为 100%、77%和 35%。此外，它比 TNM 分期系统具有更好的区分能力（C 指数：0.785，AIC：752.8708 VS. C 指数：0.712；AIC：775.1223）。甲基化诱导的 Spastic paraplegia 20 沉默通过激活 EGFR/MAPK 信号通路促进胃癌细胞增殖。基于 spartin 表达的列线图提供了比传统 AJCC TNM 分期系统更好的区分能力，为胃癌患者的生存提供了个体化的预测。
