阿贝森相互作用蛋白2在胃癌进展及预后中的作用及其调控机制
[Role of Abelson interactor 2 in progression and prognosis of gastric cancer and its regulatory mechanisms].
作者信息
Chen X, Lu H, Wang Z, Wang L, Xia Y, Geng Z, Zhang X, Song X, Wang Y, Li J, Hu J, Zuo L
机构信息
Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China.
Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Sep 20;44(9):1653-1661. doi: 10.12122/j.issn.1673-4254.2024.09.04.
OBJECTIVE
To explore the regulatory role of Abelson interactor 2 (ABI2) in progression and prognosis of gastric cancer.
METHODS
TIMER2.0, GEPIA, Kaplan-Meier Plotter and DAVID databases were used to analyze ABI2 expression in pancancer and its association with the prognosis of gastric cancer. Gastric cancer and adjacent tissues from 120 patients undergoing radical gastrectomy in our hospital between January, 2016 and October, 2018 were examined for ABI2 expression and its correlation with disease progression and prognosis. MGC-803 cell models of ABI2 knockdown and overexpression were established for observing the changes in cell proliferation, migration, and invasion, and the impact of ABI2 expression modulation on xenograft growth was evaluated in nude mice.
RESULTS
Database analysis and examination of the clinical samples showed that ABI2 was highly expressed in gastric cancer tissues. Survival analysis suggested that gastric cancer patients with a high expression of ABI2 had a reduced postoperative 5-year survival rate ( < 0.0001), and further Cox univariate and multivariate survival analyses indicated that a high ABI2 expression was an independent risk factor affecting the patients survival outcomes (=0.022, =1.887, 95% : 1.096-3.249). Enrichment analysis suggested the involvement of ABI2 in Wnt signaling. In MGC-803 cells, ABI2 overexpression promoted cell proliferation and xenograft growth in nude mice, increased the expressions of vimentin and N-cadherin, and lowered E-cadherin expression, while ABI2 knockdown produced the opposite effects. Mechanistic analysis revealed that ABI2 overexpression promoted the expressions of Wnt2 and β-catenin in both MGC-803 cells and the xenografts, and their expressions were significantly lowered by ABI2 knockdown.
CONCLUSION
ABI2 is highly expressed in gastric cancer, which affects long-term prognosis of the patients, possible due to its regulatory effect on Wnt signaling to promote proliferation, migration and invasion of gastric cancer cells.
目的
探讨阿贝尔森相互作用蛋白2（ABI2）在胃癌进展及预后中的调控作用。
方法
利用TIMER2.0、GEPIA、Kaplan-Meier Plotter和DAVID数据库分析ABI2在泛癌中的表达及其与胃癌预后的关系。检测2016年1月至2018年10月期间在我院接受根治性胃切除术的120例患者的胃癌组织及癌旁组织中ABI2的表达情况及其与疾病进展和预后的相关性。建立ABI2基因敲低和过表达的MGC-803细胞模型，观察细胞增殖、迁移和侵袭的变化，并在裸鼠中评估ABI2表达调节对异种移植瘤生长的影响。
结果
数据库分析和临床样本检测显示，ABI2在胃癌组织中高表达。生存分析表明，ABI2高表达的胃癌患者术后5年生存率降低（<0.0001），进一步的Cox单因素和多因素生存分析表明，ABI2高表达是影响患者生存结局的独立危险因素（=0.022，=1.887，95%可信区间：1.096 - 3.249）。富集分析提示ABI2参与Wnt信号通路。在MGC-803细胞中，ABI2过表达促进细胞增殖和裸鼠异种移植瘤生长，增加波形蛋白和N-钙黏蛋白的表达，降低E-钙黏蛋白的表达，而ABI2基因敲低则产生相反的效果。机制分析显示，ABI2过表达促进MGC-803细胞和异种移植瘤中Wnt2和β-连环蛋白的表达，而ABI2基因敲低则使其表达显著降低。
结论
ABI2在胃癌中高表达，影响患者的长期预后，可能是由于其对Wnt信号通路的调控作用促进了胃癌细胞的增殖、迁移和侵袭。
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