title: The expression of CXCR4 and its relationship with matrix metalloproteinase-9/vascular endothelial growth factor in esophageal squamous cell cancer.
abstract: 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.
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: C L
authors.initials: CL
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Ji
authors.forename: D
authors.initials: D
authors.lastname: Ge
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: J Y
authors.initials: JY
authors.lastname: Ding
mesh_terms: D000328:Adult; D000368:Aged; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D018307:Neoplasms, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9