Xiao Lin-Yu, Duan Ting, Xia Yong-Sheng, Chen Yue, Yan Xing-Zhou, Hu Jian-Guo
Department of Rehabilitation,The First Affiliated Hospital of Bengbu Medical University,Bengbu,Anhui 233004,China.
Department of Emergency Medicine,The First Affiliated Hospital of Bengbu Medical University,Bengbu,Anhui 233004,China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2025 Jun 30;47(3):343-353. doi: 10.3881/j.issn.1000-503X.16238.
Objective To investigate the expression of SORT1 in the gastric cancer tissue and analyze its relationship with clinical prognosis of patients as well as the pathways and mechanisms involved in gastric cancer progression.Methods The Gene Expression Profiling Interaction Analysis database,Western blot,and immunohistochemistry were employed to predict and analyze the expression of SORT1 in the gastric cancer and the adjacent tissue.The clinical case information of 109 patients who underwent radical surgery for gastric cancer in the First Affiliated Hospital of Bengbu Medical University from April 2015 to April 2017 was collected to analyze the relationship of SORT1 with the clinicopathological parameters and prognosis of the patients.Cell proliferation was detected by the CCK-8 assay and colony formation assay,while cell migration and invasion were assessed by the scratch assay and Transwell assay,respectively.Western blot was employed to determine the expression of proteins related to epithelial-mesenchymal transition(EMT)in gastric cancer cells,followed by further analysis on molecular mechanism through which SORT1 regulates EMT in gastric cancer cells.Results Western blot and immunocytochemistry results showed that SORT1 was highly expressed in the gastric cancer tissue(=0.003,<0.001),which was positively correlated with malignant progression of tumors(all <0.05).The Kaplan-Meier survival analysis revealed shortened postoperative survival periods for the patients with high expression of SORT1(<0.001).The Cox regression model indicated that SORT1 expression was an independent risk factor affecting the 5-year survival rate after surgery for gastric cancer patients(<0.001).Up-regulation of SORT1 expression promoted the proliferation,migration,invasion,and EMT of gastric cancer cells(all <0.05),while down-regulation of SORT1 showed the opposite effects(all <0.05).Western blot results showed that high expression of SORT1 promoted the expression of β-catenin,cyclin D1,and c-Myc(all <0.05).Moreover, use of the Wnt/β-catenin pathway inhibitor(XAV939)effectively suppressed the EMT enhancement caused by high expression of SORT1 in gastric cancer cells(all <0.05).Conclusions SORT1 is highly expressed in gastric cancer and affects patients' postoperative survival periods.It is involved in the proliferation,migration,and invasion of gastric cancer cells and may promote the EMT of gastric cancer cells by activating the Wnt/β-catenin pathway.
目的 探讨SORT1在胃癌组织中的表达情况，分析其与患者临床预后的关系以及在胃癌进展中涉及的途径和机制。方法 利用基因表达谱相互作用分析数据库、蛋白质免疫印迹法和免疫组织化学法预测并分析SORT1在胃癌及癌旁组织中的表达。收集2015年4月至2017年4月在蚌埠医学院第一附属医院接受胃癌根治术的109例患者的临床病例资料，分析SORT1与患者临床病理参数及预后的关系。采用CCK-8法和集落形成试验检测细胞增殖，划痕试验和Transwell试验分别评估细胞迁移和侵袭能力。运用蛋白质免疫印迹法检测胃癌细胞中与上皮-间质转化（EMT）相关蛋白的表达，进而分析SORT1调控胃癌细胞EMT的分子机制。结果 蛋白质免疫印迹法和免疫组织化学结果显示，SORT1在胃癌组织中高表达（P = 0.003，P < 0.001），与肿瘤恶性进展呈正相关（均P < 0.05）。Kaplan-Meier生存分析显示，SORT1高表达患者术后生存期缩短（P < 0.001）。Cox回归模型表明，SORT1表达是影响胃癌患者术后5年生存率的独立危险因素（P < 0.001）。上调SORT1表达促进胃癌细胞的增殖、迁移、侵袭及EMT（均P < 0.05），而下调SORT1表达则产生相反作用（均P < 0.05）。蛋白质免疫印迹结果显示，SORT1高表达促进β-连环蛋白、细胞周期蛋白D1和c-Myc的表达（均P < 0.05）。此外，使用Wnt/β-连环蛋白通路抑制剂（XAV939）可有效抑制SORT1高表达引起的胃癌细胞EMT增强（均P < 0.05）。结论 SORT1在胃癌中高表达，影响患者术后生存期，参与胃癌细胞的增殖、迁移和侵袭，可能通过激活Wnt/β-连环蛋白通路促进胃癌细胞的EMT。
