Jia Yong-Xu, Li Teng-Fei, Zhang Dan-Dan, Fan Zong-Min, Fan Hui-Jie, Yan Jie, Chen Li-Juan, Tang Hong, Qin Yan-Ru, Li Xing-Ya
Department of Oncology, The First Affiliated Hospital of Zhengzhou University; Esophageal and Gastric Cancer Center of Henan Province.
Department of Interventional Radiology.
Onco Targets Ther. 2016 Sep 27;9:5919-5929. doi: 10.2147/OTT.S111778. eCollection 2016.
Molecular-targeted therapy against tyrosine kinase receptors (RTKs) plays an important role in gastric cancer (GC) treatment. Understanding the correlation between RTK coexpression could better guide clinical drug use. In the present study, the coexpression status of c-MET, fibroblast growth factor receptor 2 (FGFR2), and human epidermal growth factor receptor 2 (HER2) in human GC and their clinical significance in clinical therapy were explored. Immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction and fluorescent in situ hybridization were performed in 143 cases of GC who had undergone gastrectomy without preoperative chemoradiotherapy. Their association with clinicopathological features and clinical prognosis was analyzed. The frequencies of c-MET, FGFR2, and HER2 overexpression were 47.6% (68/143), 34.3% (49/143), and 10.5% (15/143), respectively. In the RTK coexpression study, 30.1% of patients (43/143) were positive for only one RTK, 25.8% (37/143) were positive for two RTKs, 3.5% (5/143) had triple-positive status, and 40.6% (58/143) had triple-negative status. In survival analysis, the overexpression of c-MET, FGFR2, and HER2 were significantly associated with overall survival (OS) (=0.018, 0.004, and 0.049, respectively). In coexpression analysis, patients with triple-positive GC had the poorest OS (=0.013). In conclusion, RTK coexpression is significantly associated with poor clinical outcome in GC.
针对酪氨酸激酶受体(RTKs)的分子靶向治疗在胃癌(GC)治疗中发挥着重要作用。了解RTK共表达之间的相关性可以更好地指导临床用药。在本研究中,探讨了人GC中c-MET、成纤维细胞生长因子受体2(FGFR2)和人表皮生长因子受体2(HER2)的共表达状态及其在临床治疗中的临床意义。对143例未接受术前放化疗而行胃切除术的GC患者进行免疫组织化学(IHC)染色、定量实时聚合酶链反应和荧光原位杂交。分析它们与临床病理特征和临床预后的关系。c-MET、FGFR2和HER2过表达的频率分别为47.6%(68/143)、34.3%(49/143)和10.5%(15/143)。在RTK共表达研究中,30.1%的患者(43/143)仅一种RTK呈阳性,25.8%(37/143)两种RTK呈阳性,3.5%(5/143)为三阳性状态,40.6%(58/143)为三阴性状态。在生存分析中,c-MET、FGFR2和HER2的过表达与总生存期(OS)显著相关(分别为=0.018、0.004和0.049)。在共表达分析中,三阳性GC患者的OS最差(=0.013)。总之,RTK共表达与GC患者不良临床结局显著相关。