the coexpression and prognostic significance of c-met, fibroblast growth factor receptor 2, and human epidermal growth factor receptor 2 in resected gastric cancer: a retrospective study

Yong-Xu Jia,1,2,* Teng-Fei Li,3,* Dan-Dan Zhang,4 Zong-Min Fan,5 Hui-Jie Fan,1,2 Jie Yan,1,2 Li-Juan Chen,6 Hong Tang,6 Yan-Ru Qin,1,2 Xing-Ya Li1 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 2Esophageal and Gastric Cancer Center of Henan Province, 3Department of Interventional Radiology, 4Department of Pathology, 5Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, 6Department of Oncology, Tumor Hospital of Henan Province, Zhengzhou, Henan, People’s Republic of China *These authors contributed equally to this work Abstract: 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) (P=0.018, 0.004, and 0.049, respectively). In coexpression analysis, patients with triple-positive GC had the poorest OS (P=0.013). In conclusion, RTK coexpression is significantly associated with poor clinical outcome in GC. Keywords: c-MET, FGFR2, HER2, gastric cancer, coexpression, survival, target therapy