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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 investigate the expression of human epidermal growth factor receptor 3 (HER3) in human gastric cancer and gastric cancer cell lines. Methods A retrospective analysis of 161 cases of gastric cancer patients, immunohistochemical analysis of HER3 expression. Small interfering RNA (siRNA) against human HER3 gene was constructed and transfected into gastric cancer cell lines with high expression of HER3. The proliferation, migration and apoptosis of gastric cancer cell lines were detected before and after transfection. Results The high expression of HER3 was correlated with the depth of tumor invasion, lymph node metastasis, staging, invasion of vascular vessel and prognosis (P <0.05 or P <0.01). Multivariate analysis showed that HER3 overexpression was an independent predictor of gastric cancer (HR: 1.922, 95% CI: 1.081-3.416, P = 0.026) in the staging of cancer (HR: 4.044,95% CI: 2.149-7.609, P = 0.000) ). HER3 siRNA treatment of gastric cancer cell lines, HER3 downregulation, gastric cancer cell proliferation (72h, MNK45vs.MNK45siRNA, SGC7901vs.SGC7901siRNA: P <0.05; 96h, MNK45vs.MNK45siRNA: P <0.05, SGC7901vs.SGC7901siRNA: P <0.01) , Migration was inhibited (P = 0.0071), apoptosis increased (MNK45vs.MNK45 siRNA: P = 0.0019; SGC7901vs.SGC7901siRNA: P = 0.0061). Conclusion HER3 is closely related to the malignant phenotype of gastric cancer, which is an independent indicator of poor prognosis of gastric cancer and may become a new therapeutic target.