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Prognostic significance of expression of cysteine-rich 61 and cyclooxygenase-2 in gastric cancer. BACKGROUND: This study aimed to evaluate the clinical significance of cysteine-rich 61 (Cyr-61/CCN1) and cyclooxygenase-2 (COX-2), and further explored their combined prognostic significance in gastric cancer. METHODS: This retrospective study examined the expressions of Cyr-61 and COX-2 in 82 surgically removed gastric cancer specimens and 43 non-tumor gastric mucosa specimens by immunohistochemical staining to identify the abnormal expression of Cyr-61 or COX-2 in gastric cancer. Crude survival curves were constructed by the Kaplan-Meier method and Cox proportional hazards regression analysis was performed to confirm the prognostic roles of Cyr-61/COX-2 as well as sex and histological grade. RESULTS: The expressions of Cyr-61 (p < 0.001) and COX-2 (p = 0.001) were both significantly up-regulated in gastric cancer samples compared with non-tumor gastric mucosa samples. The high expression of Cyr-61 or COX-2 was associated with invasion, lymph node metastasis, distant metastases, poor histological differentiation, advanced TNM stage and lower 5-year survival rate (all p < 0.05). Both Cyr-61 and COX-2 high expressions [hazard ratio (HR) = 31.8, 95 % confidence interval (CI) 4.09-246.8] was associated the higher risk of death during 5 years follow up than single Cyr-61 high expression (HR = 4.1, 95 % CI 1.5-11.6) or COX-2 high expression (HR = 2.9, 95 % CI 1.06-7.8). CONCLUSIONS: Cyr-61 and COX-2 expressions are associated with the progression of gastric cancer. Additionally, combined expressions of Cyr-61 and COX-2 has a higher prognostic value than single expression.