Overexpression of CD88 predicts poor prognosis in non-small-cell lung cancer
Overexpression of CD88 predicts poor prognosis in non-small-cell lung cancer
复制标题
CD88 过度表达预示非小细胞肺癌预后不良
DOI：
10.1016/j.lungcan.2013.04.020
复制
发表时间：
2013-08-01
期刊：
影响因子：
5.3
通讯作者：
Ge, Di
中科院分区：
文献类型：
--
作者：
Gu, Jie;Ding, Jian-yong;Ge, Di
CD88(C5aR)是一种G蛋白偶联受体，因其在多种炎症性疾病中的作用而广为人知，但其在肿瘤发生中的作用尚不清楚。在这项研究中，我们研究了CD88在非小细胞肺癌(NSCLC)患者手术切除后的预后价值。以5个非小细胞肺癌细胞系和1个正常支气管上皮细胞系为研究对象，从mRNA水平分析CD88的表达。采用免疫组织化学方法检测208例非小细胞肺癌组织芯片(TMA)中CD88和E-钙粘附素的表达。结果表明，CD88在NSCLC细胞中的表达明显高于正常支气管上皮细胞，与癌旁非肿瘤肺组织相比，CD88蛋白在NSCLC组织中过表达。此外，高水平的CD88与非小细胞肺癌患者的淋巴转移相关(p=0.012)。CD88高表达患者的5年总生存期显著低于CD88低表达患者(p=0.001)，多因素分析显示CD88表达是影响患者总生存的独立预后因素(HR=1.614，95%CI 1.082~2.407，p=0.019)。最后，我们证实CD88的表达与E-钙粘素的表达呈负相关(p<；0.001)。干扰CD88表达可抑制肺癌细胞的迁移，上调E-钙粘蛋白的表达。因此，我们的结果表明CD88在非小细胞肺癌中高表达。CD88高水平与非小细胞肺癌术后预后不良相关，并通过下调E-钙粘附素促进肿瘤转移。CD88可作为一种潜在的预后标志物，用于筛选预后不良患者。(C)2013爱思唯尔爱尔兰有限公司。保留所有权利。
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 CD88(high) was significantly lower than-those in the CD88(low) group (p = 0.001), and multivariate analysis revealed that CD88 expression was an independent prognostic factor in patients' overall survival (HR = 1.614, 95% Cl 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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.