HER3高表达与胃癌恶性表型的关系

Relationship between overexpression of HER3 and malignant phenotype of gastric cancer

目的探讨人表皮生长因子受体3(HER3)在人胃癌组织及胃癌细胞株中的表达。方法回顾性分析胃癌患者161例,应用免疫组化方法分析HER3表达。构建针对人HER3基因的小干扰RNA(siRNA),对HER3高表达的胃癌细胞株进行转染,检测转染前后胃癌细胞株增殖、迁移率、凋亡率变化。结果 HER3高表达与肿瘤浸润深度、淋巴结转移、分期、神经脉管侵犯及预后有关(P<0.05或P<0.01)。多因素分析显示:肿瘤分期(HR:4.044,95%CI:2.149-7.609,P=0.000)、HER3高表达是胃癌独立的预后因素(HR:1.922,95%CI:1.081-3.416,P=0.026)。HER3siRNA处理胃癌细胞株后,HER3表达下调,胃癌细胞株增殖(72h时,MNK45vs.MNK45siRNA,SGC7901vs.SGC7901siRNA:P<0.05;96h时,MNK45vs.MNK45siRNA:P<0.05,SGC7901vs.SGC7901siRNA:P<0.01)、迁移受抑制(P=0.0071),凋亡增加(MNK45vs.MNK45siRNA:P=0.0019;SGC7901vs.SGC7901siRNA:P=0.0061)。结论 HER3与胃癌恶性表型密切相关,是胃癌预后不良的独立指标之一,有可能成为治疗新靶点。

Objective To study the relationship between overexpression of human epidermal growth factor receptor 3（HER3） and malignant phenotype of gastric cancer. Methods The expression of HER3 was detected by irmnunohistochemistry in 161 patients with gastric cancer underwent gastrectomy. Clinicopathological characteristics and the expression of HER3 were retrospectively analyzed. HER3 siRNA was constructed and transfected to human gastric cancer cell with HER3 expression. The expression of HER3 was detected by Western blot assay, the proliferation of the cells by MTT assay, the invasion by wound-healing assay, and the apoptosis by TUNEL assay. Results The high expression of HER3 was associated with tumor invasive depth, lymph node metastasis, stage,the invasion of nerve and vessel, and the 4-year overall survival（P〈0.05 or P〈0. 01）. The independent prognostic factors were the stage （HR.. 4. 044, 95% CI： 2. 149-7. 609, P=0. 000） and overexpression of HER3（HR： 1. 922,95%CI： 1. 081-3. 416, P=0. 026）. In vitro, expression of HER3 was significantly inhibited by HER3 siRNA. The proliferation（72 h： MNK45 vs. MNK45 siRNA, SCK;7901 vs. SGC7901 siRNA： P〈0. 05,96 h： MNK45 vs. MNK45 siRNA： P〈0. 05, SGC7901 vs. 8GC7901 siRNA： P〈0.01） and the invasion （P=0.0071） of gastric cancer cells were down- regulated and the apoptosis（MNK45 vs. MNK45 siRNA： P=0. 0019,SGC7901 vs. SCC7901 siRNA： P=0. 0061） of the cells was significantly increased after treated with HER3 siRNA. Conclusion In gastric cancer, the overexpression of HER3 is associated with the proliferation, invasion, and apoptosis of gastric cancer. High expression of HER3 predicts a poor survival in the patients with gastriccancer.