The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215006, P.R. China.
Sci Rep. 2018 Jan 10;8(1):397. doi: 10.1038/s41598-017-17435-6.
HER2 becomes the standard of care for guiding adjuvant treatment of gastric cancer with trastuzumab in recent years. However, the usage of this target agent is still limited because of the resistance to trastuzumab or the negative expression of HER2 in tumor tissues. The Gli1 and HER2 both play an important role in the pathogenesis of gastric cancer. However, the correlation of them is still unclear. Here we found Gli1 and HER2 are highly expressed in gastric cancer tissues, and they are positively related. Next, we found Gli1 positive patients live a shorter survival time no matter HER2 positive or negative. Furthermore, univariate and multivariate analysis revealed that venous invasion, HER2 expression, Gli1 expression were independent prognostic factors for the survival time in gastric cancer. In addition, suppressing the expression level of Gli1 can decrease the cell viability and migration ability in cells and subcutaneous tumors. Finally, we found that HER2 may regulate Gli1 by Akt-mTOR-p70S6K pathway. Inhibit of HER2 and SMO have synergistic effect on reduction of cell viability. In conclusion, Gli1 is a favorable prognostic indicator in gastric cancer. As a novel target, Gli1 worth further study, especially in Her2-targeted therapy-resistant cancers.
近年来，HER2 已成为指导胃癌曲妥珠单抗辅助治疗的标准。然而，由于对曲妥珠单抗的耐药性或肿瘤组织中 HER2 的阴性表达，该靶向药物的应用仍然受到限制。Gli1 和 HER2 在胃癌的发病机制中均发挥重要作用。然而，它们之间的相关性尚不清楚。本研究发现 Gli1 和 HER2 在胃癌组织中高表达，且呈正相关。进一步分析发现，无论 HER2 表达阳性或阴性，Gli1 阳性患者的生存时间均较短。单因素和多因素分析显示，静脉侵犯、HER2 表达、Gli1 表达是胃癌患者生存时间的独立预后因素。此外，抑制 Gli1 的表达水平可降低细胞活力和迁移能力，在体内和皮下肿瘤中均有此作用。最后，我们发现 HER2 可能通过 Akt-mTOR-p70S6K 通路调节 Gli1。抑制 HER2 和 SMO 对降低细胞活力具有协同作用。综上所述，Gli1 是胃癌的一个有利预后指标。作为一种新的靶点，Gli1 值得进一步研究，尤其是在针对 Her2 靶向治疗耐药的癌症中。
