The signaling pathway of Wnt/β-catenin is considered a hallmark of cancer development in gastric cancer .It facilitates cancer stem progression, thus leads to metastasis and therapy response resistance. Therefore, the therapeutic potential of agents targeting this signaling pathway in cancer is a challenge. Aim of the study: Evaluation the relationships between clinicopathological characteristics of gastric cancer patients, disease progression and therapy response with HMGA1, c-Cbl and TNFRSF11B expressions were analyzed. The expressions of HMGA1, in gastric cancer were correlated with the tumor size, LN metastases, stage, mortality and recurrence P(0.038, <0.001,0.006, 0.006 and 0.004) respectively ,the expression of TNFRSF11B was significantly correlated with age, grade, stage ,LN metastases, stage AJCC, mortality and recurrence P( 0.024, <0.001, 0.01, <0.001, 0.003, 0.002 and 0.003) respectively,low C-cbl expression was significantly correlated with tumor size, grade, stage, LN metastasis and AJCC staging.Moreover, the OS of patients with high HMGA1 and TNFRSF11B -strong tumors was significantly lower than that of patients with negative tumors (p =, 005 Vs p=0.004) respectively. However, the expression of low c-Cbl in GC was correlated with de-differentiation, advanced stage, lymph nodes metastasis, and distant metastases (p=0.004). However, High c-Cbl expression was linked with no tumor recurrence (p=0.002) and favorable survival rates (p <0.001). Up-regulation of HMGA1 and TNFRSF11B had a significant association with poor clinical response to the therapy respectively. However that high c-Cbl expression is related to good response to therapy (p=0.002) . The HMGA1 and TNFRSF11B over expression had an essential role in gastric cancer development and progression. C-Cbl expression negatively correlates with tumor infiltration and metastasis in lymph node so they play role in prognosis and clinical response prediction in GC patients.