Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Dis Esophagus. 2011 May;24(4):283-90. doi: 10.1111/j.1442-2050.2010.01135.x. Epub 2010 Nov 18.
Esophageal cancer (EC) is a highly aggressive neoplasm with poor prognosis. The main reason for this disappointing outcome is the strong behavior of esophageal cancer cell's invasion and metastasis. CXC chemokine receptor 4 (CXCR4) was found to be expressed in many tumors and significantly correlated with invasion, angiogenesis, metastasis, and prognosis. In the present study, we investigated the expressions of CXCR4, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor (VEGF) in esophageal squamous cell cancer (ESCC) and analyzed the relationship among the three proteins. Sections of paraffin-embedded tissues were obtained from 127 patients with ESCC undergoing esophagectomy at Zhongshan Hospital, Fudan University in 2005. The CXCR4, MMP-9, and VEGF expressions in EC tissues were evaluated according to the immunohistochemical staining area and intensity. The correlations between patients' prognosis and covariates were analyzed by Kaplan--Meier method (univariate analysis) and Cox regression (multivariate analysis). The overall expression rate of CXCR4, MMP-9, and VEGF was 88.2%, 93.7%, and 79.5%, respectively. CXCR4 expression was significantly associated with tumor grade, tumor size, tumor depth, regional lymph node metastasis, and tumor, node, metastasis (TNM) stage (P < 0.05). MMP-9 expression was significantly associated with age and tumor grade (P < 0.05). VEGF expression was significantly associated with tumor grade, tumor depth, and TNM stage (P < 0.05). CXCR4 expression was positively correlated with MMP-9 expression (P < 0.01, r= 0.365) and VEGF expression (P < 0.01, r= 0.380). However, there was no significant correlation between MMP-9 and VEGF expression (P > 0.05). In univariate analysis, CXCR4 expression, tumor size, tumor depth, lymph node metastasis, and TNM stage were correlated with patients' prognosis (P < 0.05); in multivariate analysis, tumor size and lymph node metastasis were the independent factors of poor prognosis. CXCR4 was highly expressed in ESCC and correlated with MMP-9, VEGF, clinicopathological features and prognosis. We speculated CXCR4 play an important role during the progression of this disease and there might be some regulatory mechanism existing between CXCR4 and MMP-9/VEGF in ESCC.
食管癌（EC）是一种侵袭性强、预后差的恶性肿瘤。导致这种不良结果的主要原因是食管癌细胞侵袭和转移的强烈行为。已经发现 CXC 趋化因子受体 4（CXCR4）在许多肿瘤中表达，并与侵袭、血管生成、转移和预后显著相关。在本研究中，我们研究了 CXCR4、基质金属蛋白酶 9（MMP-9）和血管内皮生长因子（VEGF）在食管鳞状细胞癌（ESCC）中的表达，并分析了这三种蛋白之间的关系。从 2005 年在复旦大学中山医院接受食管切除术的 127 名 ESCC 患者的石蜡包埋组织切片中获得组织。根据免疫组织化学染色面积和强度评估 EC 组织中的 CXCR4、MMP-9 和 VEGF 表达。通过 Kaplan-Meier 方法（单因素分析）和 Cox 回归（多因素分析）分析患者预后与协变量之间的相关性。CXCR4 表达与肿瘤分级、肿瘤大小、肿瘤深度、区域淋巴结转移和肿瘤、淋巴结、转移（TNM）分期显著相关（P<0.05）。MMP-9 表达与年龄和肿瘤分级显著相关（P<0.05）。VEGF 表达与肿瘤分级、肿瘤深度和 TNM 分期显著相关（P<0.05）。CXCR4 表达与 MMP-9 表达呈正相关（P<0.01，r=0.365）和 VEGF 表达呈正相关（P<0.01，r=0.380）。然而，MMP-9 和 VEGF 表达之间无显著相关性（P>0.05）。单因素分析显示，CXCR4 表达、肿瘤大小、肿瘤深度、淋巴结转移和 TNM 分期与患者预后相关（P<0.05）；多因素分析显示，肿瘤大小和淋巴结转移是预后不良的独立因素。CXCR4 在 ESCC 中高表达，并与 MMP-9、VEGF、临床病理特征和预后相关。我们推测 CXCR4 在疾病进展过程中发挥重要作用，并且在 ESCC 中可能存在 CXCR4 与 MMP-9/VEGF 之间的调节机制。
