Objective:To investigate the expression of osteopontin(OPN)and caudal-related homeobox gene 2(CDX2)in advanced gastric cancer,and to correlate them with clinicopathological features.Method:One-hundred and nine patients suffered from gastric cancer recruited.Expression of OPN and CDX2 and other molecular markers were determined using immunohistochemistry method.Results:Total positive rate of OPN expression was 46.79%,and related with depth of cancer invasion and different phenotype(P<0.001),no association with the patient’s age,gender,tumor histological type and lymph node metastasis.In different phenotypes of gastric cancers,OPN frequently expressed in CDX2-negative-expressed G and N type(16/109 and 21/109,respectively),and in CDX2-positive-expressed GI and I types expression level were lower.OPN expression reversely correlated with cdx-2 expression(P<0.001).Patients with OPN positive expression had worse 5-year survival,and patients with OPN negative,5-year survival time better(P<0.001).Further analysis revealed patients with OPN-/CDX2+ had better 5-year survival than other three groups including OPN+/CDX2-,OPN-/CDX2-and OPN+/CDX2+.With multivariate analysis for 5-year survival,it suggested that OPN was the most significant predictor of poor prognosis in gastric cancer(P =0.0043),with lymph node metastasis and tumor depth of invasion were also independent indicators(P =0.0359 and P =0.0315,respectively).Conclusion:Osteopontin is a useful prognostic marker in gastric cancer,and combined with CDX2,it may be much more useful for predicting the survival time in advanced gastric cancer patients.Furthermore it also gave us a clue that in gastric cancer,CDX2 may be a transcription factor modulating the expression of osteopontin. Objective: To investigate the expression of osteopontin (OPN) and caudal-related homeobox gene 2 (CDX2) in advanced gastric cancer, and to correlate them with clinicopathological features. Method: One-hundred and nine patients suffered from gastric cancer recruited. Expression of Results: Total positive rate of OPN expression was 46.79%, and related with depth of cancer invasion and different phenotype (P <0.001), no association with the patient’s age, gender, tumor histological type and lymph node metastasis. In different phenotypes of gastric cancers, OPN frequently expressed in CDX2-negative-expressed G and N type (16/109 and 21/109, respectively), and in CDX2-positive-expressed GI and I (P <0.001). Patients with OPN positive expression had worse 5-year survival, and patients with OPN negative, 5-year survival time better (P <0.00) 1) .Further analysis revealed patients with OPN- / CDX2 + had better 5-year survival than the other three groups including OPN + / CDX2-, OPN- / CDX2- and OPN + / CDX2 + .With multivariate analysis for 5-year survival, it suggested that OPN was the most significant predictor of poor prognosis in gastric cancer (P = 0.0043), with lymph node metastasis and tumor depth of invasion were also independent indicators (P = 0.0359 and P = 0.0315, respectively) .Conclusion: Osteopontin is a useful prognostic marker in gastric cancer, and combined with CDX2, it may be much more useful for predicting the survival time in advanced gastric cancer patients. F urthermore it also gave us a clue that in gastric cancer, CDX2 may be a transcription factor modulating the expression of osteopontin .