Abstract
Chemokine stromal cell-derived factor (SDF)-1α and its receptor CXC chemokine receptor 4 (CXCR4) have been shown to impact cancer progression. Accumulating evidence suggests that CXCR4 and SDF-1α expression is useful for evaluating the risk of gastric cancer progression. Thus, combined analysis of SDF-1α and CXCR4 should have high prognostic potential as a molecular marker for gastric cancer. We investigated the expression of SDF-1α and CXCR4 using immunohistochemistry in relation to prognosis, clinicopathological features and clinical outcomes in 221 cases of primary gastric cancer. Patients were categorized into three groups according to CXCR4 and SDF-1α expression: high CXCR4/high SDF-1α, low CXCR4/low SDF-1α, and high CXCR4/low SDF-1α - low CXCR4/high SDF-1α. No significant differences were noted in age, gender, histology, tumor location, lymphovascular invasion or proportion of tumor size >5 cm among the three groups. However, high CXCR4/high SDF-1α expression in tumor cells was significantly associated with depth of invasion of the tumor, lymph node involvement, and higher tumor stage compared to tumors with low CXCR4/low SDF-1α expression or high CXCR4/low SDF-1α - low CXCR4/high SDF-1α expression. Furthermore, patients with high CXCR4/high SDF-1α expression had the worst patient prognosis, whereas patients who had low CXCR4/low SDF-1α expression showed the most favorable prognosis. In conclusion, CXCR4 and SDF-1α are useful prognostic factors in gastric cancer, and the combination of high CXCR4 protein expression with high SDF-1α expression suggests a dismal prognosis.