Abstract
ABSTRACT Background Chemokines and their receptors have been shown to play a critical role in cancer growth and metastasis. In particular, recent data have suggested that the chemokine CXCL12 and its receptor CXCR7 (also known as RDC1), which has been recently identified as a chemokine receptor, have key functions in promoting tumor development and progression. However, there is little information regarding their expression and clinical relevance in gastric cancer. Here we investigated for the first time the effects of combined CXCR7 and CXCL12 expression on the prognosis of patients with gastric cancer. Methods We studied CXCL12 and CXCR7 protein expression in 221 specimens of primary gastric cancer using immunohistochemistry, and investigated the relationaship between CXCL12/CXCR7 expression and clinicopathological features and clinical outcomes. Results Patients were categorized into four groups according to CXCR7 and CXCL12 expression: low CXCR7/low CXCL12, high CXCR7/low CXCL12, low CXCR7/high CXCL12, and high CXCR7/high CXCL12. No significant differences existed in age, gender, histology, tumor location, lymphovascular invasion among the four groups. However, high CXCR7/high CXCL12 expression in tumor cells was significantly associated with invasion depth of the tumor (T status; P 5 cm (P = 0.006) compared to tumors with low CXCR7/low CXCL12 expression or high CXCR7/low CXCL12–low CXCR7/high CXCL12 expression. Furthermore, patients with high CXCR7/high CXCL12 expression had the worst prognosis (5-year survival rate 30.6%; median, 2.3 years; range, 0.1 - 5.7 years) compared to those of other patient groups (5-year survival rate, 52.4%; median, not reached; log-rank test, P = 0.008) . Conclusions CXCR7 and CXCL12 are useful prognostic factors in gastric cancer, and the combination of high CXCR7 protein expression with high CXCL12 expression suggests a dismal prognosis. Disclosure All authors have declared no conflicts of interest.
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