Overexpression of CD88 predicts poor prognosis in non-small-cell lung cancer

Abstract

CD88 (C5aR), a G-protein-coupled receptor, is well known as it functions in various inflammatory diseases, however, its role in tumorigenesis remains unclear. In this study we investigated the prognostic value of CD88 in patients with non-small-cell lung cancer (NSCLC) after surgical resection. Five NSCLC cell lines and one normal bronchial epithelial cell line were used to analyze the CD88 expression at the mRNA level. Then, the expression of CD88 and E-cadherin were further examined by immunohistochemistry (IHC) in tissue microarray (TMA) consisting of 208 cases of NSCLSs. Data revealed that CD88 expression was significantly higher in NSCLC cells than that in normal bronchial epithelial cells, and compared with the adjacent non-tumorous lung tissues, the CD88 protein overexpressed in NSCLC tissues. Furthermore, high levels of CD88 were found to be correlated with lymph node metastasis in NSCLC patients (p=0.012). The 5-year overall survival of patients with CD88high was significantly lower than those in the CD88low group (p=0.001), and multivariate analysis revealed that CD88 expression was an independent prognostic factor in patients’ overall survival (HR=1.614, 95% CI 1.082–2.407, p=0.019). Finally, we confirmed the CD88 expression negatively correlated with E-cadherin expression (p<0.001). Interference of CD88 expression impaired the migration of lung cancer cells and up-regulated the E-cadherin protein expression. Thus, our results indicate that CD88 is overexpressed in NSCLC. High levels of CD88 are associated with poor prognosis of NSCLC after resection and promote tumor metastasis via down-regulation of E-cadherin. CD88 can be a potential prognostic marker to screen patients for unfavorable prognosis.