Prognostic impact of atypical chemokine receptor expression in patients with gastric cancer.

BACKGROUND: Atypical chemokine receptors (ACRs), which serve as a decoy receptor to attract chemokines, including DARC, D6, and CCX-CKR, have an important role in inhibiting invasion and metastasis of cancer cells; however, their expression in gastric cancer has not been characterized. The purpose of this study was to determine the predictive value of ACRs for overall survival in gastric cancer.

METHODS: We performed immunohistochemical analysis on formalin-fixed, paraffin-embedded cancer tissue and used Western blot analysis on cell lines with an antibody against ACR protein. We investigated tumor material from total of 282 consecutive gastric specimens, composed of 101 normal gastric tissues, 181 peri-carcinoma tissues (2 cm away from the carcinoma), and their relationships to clinicopathologic features and survival, using a tissue micro-array.

RESULTS: We found the expression of ACRs to be lower in gastric cancer cell lines or tissues than in normal cell line, peri-carcinoma, or normal tissues, respectively (P < 0.05). In univariate analysis, the three proteins and their co-expression were significantly associated with higher overall survival. In multivariate analysis, each of these molecules was not favorable for overall survival; however, their co-expression was an independently prognostic factor for overall survival (hazard ratio, 0.276; 95% confidence interval, 0.173-0.444; P < 0.001).

CONCLUSIONS: These findings highlight the possibility that the multiple loss of ACRs may occur during the development of tumorigenesis, and their co-expression in gastric cancer may be predictive of favorable outcomes.