Expression Of Eph Genes In Gastric Cancer And Its Impact On Prognosis And Chemotherapy Response

Gastric cancer is one of the most common cancer worldwide with high incidence and mortality. However, its clinical outcome still remains unsatisfactory. To explore the molecular mechanism of carcinogenesis and progression might improve its early detection, treatment and clinical outcome, and might also help to find new prognostic factors. Eph receptors constitute the largest sub-family of receptor tyrosine kinases (RTKs), including 16 receptors and 9 ligands, which are grouped into two subclasses depending on their ligand specificity. These receptors are involved in a wide range of processes directly related with tumorigenesis, metastasis and even angiogenesis. Currently, research about Eph genes in gastric cancer is relatively less. This research aimed to detect the expression of Eph genes in gastric cancer and explore its impact on prognosis and response of drug therapy.Part 1 Expression of Eph genes in gastric cancer and its clinicopathological significanceObjective: This study aimed to analyze the expression of EphA1,Eph A7 and EphB1 genes in gastric cancer and its correlation with clinical parameters, so as to explore the significance of them in the etiology and progression in gastric cancer.Methods: Expression of EphA1, EphA7 was determined using real time RT-PCR and immunohistochemical staining in 65 gastric cancer patients, so was expression of EphB1 in 58 patients. Correlation between EphA1,EphA7 and EphB1 expression and clinical parameters was measured by statistics.Results: EphA1, EphA7 and EphB1 genes expressed aberrantly in this group of patients. Expression of EphA1 mRNA and protein were related to lymphatic stages (P=0.011, 0.040, respectively) and TNM stages (P=0.014, 0.028, respectively). Expression of EphA7 mRNA was related to lymphatic stages (P=0.024) and TNM stages (P=0.048), and expression of EphA7 protein was related to TNM stages (P=0.029). Expression of EphB1 mRNA was related to lymphatic stages (P=0.045), and expression of EphB1 protein was related to lymphatic stages (P=0.043) and TNM stages (P=0.001).Conclusion: These data imply that EphA1, EphA7 genes could promote the progression of gastric cancer, and EphB1 gene could inhibit progression of gastric cancer. Part 2 Expression of Eph Genes and Prognosis of Gastric CancerObjective: This part of study aimed to analyze the relation between expression of EphA1, EphA7 and EphB1 genes and the prognosis of patients with gastric cancer.Methods: Patients in part 1 were followed up. Univariate and multivariate survival analysis was carried out between the prognosis of the patients and expression of EphA1, EphA7 and EphB1 genes and other clinical factors.Results: Univariate analysis showed that overall survival was related to expression of EphA1 mRNA (P=0.001), EphA1 protein (P=0.029), EphA7 mRNA (P=0.012) and EphA7 protein (P=0.001), and patients with over expression of EphA1 or EphA7 had relatively poor prognosis. Overall survival was related to tumor residual status (P=0.000), lymphatic stage (P=0.000) and final TNM stage (P=0.001). Disease free survival was related to EphA1 mRNA (P=0.001), EphA1 protein (P=0.028), EphA7 mRNA (P=0.013), EphA7 protein (P=0.002), and patients with over expression of EphA1 or EphA7 had earlier tumor recurrence. Disease free survival was also related to tumor residual status (P=0.000), lymphatic stage (P=0.000) and final TNM stage (P=0.001). Multivariate survival analysis showed that expression of EphA1 mRNA, final TNM stage and tumor residual status may be independent prognostic factors.Conclusion: Expression of EphA1 and EphA7 was related to survival and might be potential prognostic factors. Expression of EphB1 did not have a clear impact on survival, so it needs further study. Part 3 Expression of Eph Genes and Tumor Response to Neoadjuvant chemotherapyObjective: To analyze the relation between expression of EphA1 and EphA7 protein in gastric cancer and tumor response to neoadjuvant chemotherapy. To observe the impact of neoadjuvant chemotherapy on expression of EphA1 and EphA7 protein at mean time.Methods: We treated 55 advanced gastric cancer patients with severe lymph node metastasis with neoadjuvant chemotherapy of FLEEOX regimen. Expression of EphA1 and EphA7 protein was examined by immunohistochemistry staining on tumor tissue both before and after neoadjuvant chemotherapy. Tumor response to neoadjuvant chemotherapy was evaluated by abdominal CT and pathological sections. Relation between expression of EphA1 and EphA7 protein and response to chemotherapy was analyzed.Results: Expression of EphA1 protein was related to response rate of both imageology (P=0.044) and pathology (P=0.018), and patients with over expression of EphA1 had better response to chemotherapy. There was no significant statistical relation between expression of EphA7 protein and response rate. This study also showed neoadjuvant chemotherapy downgraded expression of EphA1 and EphA7 protein.Conclusion: EphA1 might be a potential predictive marker of tumor response to neoadjuvant chemotherapy of gastric cancer. Neoadjuvant chemotherapy could downgraded expression of EphA1 and EphA7 protein.ConclusionEphA1 and EphA7 genes may promote the progression of gastric cancer, and be related to survival. EphA1 protein was related to tumor response to chemotherapy and might be a potential predictive marker to neoadjuvant chemotherapy. EphB1 protein might inhibit the progression of gastric cancer, but its influence on prognosis remains further study.