title: The expressions of MIF and CXCR4 protein in tumor microenvironment are adverse prognostic factors in patients with esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Tumor-derived cytokines and their receptors usually take important roles in the disease progression and prognosis of cancer patients. In this survey, we aimed to detect the expression levels of MIF and CXCR4 in different cell populations of tumor microenvironments and their association with survivals of patients with esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  MIF and CXCR4 levels were measured by immunochemistry in tumor specimens from 136 resected ESCC. Correlation analyses and independent prognostic outcomes were determined using Pearson's chi-square test and Cox regression analysis.
  
  
  RESULTS
  The expression of CXCR4 in tumor cells was positively associated with tumor status (P = 0.045) and clinical stage (P = 0.044); whereas the expression of CXCR4 in tumor-infiltrating lymphocytes (TILs) and the expression of MIF in tumor cells and in TILs were not associated with clinical parameters of ESCC patients. High MIF expression in tumor cells or in TILs or high CXCR4 expression in tumor cells was significantly related to poor survival of ESCC patients (P < 0.05). Multivariate analysis showed that the expression of MIF or CXCR4 in tumor cells and the expression of MIF in TILs were adverse independent factors for disease-free survival (DFS) and overall survival (OS) in the whole cohort of patients (P < 0.05). Furthermore, the expression of MIF and CXCR4 in tumor cells were independent factors for reduced DFS and OS in metastatic/recurrent ESCC patients (P < 0.05). Interestingly, the expressions of MIF and CXCR4 in tumor cells and in TILs were significantly positively correlated (P < 0.05), and the combined MIF and CXCR4 expression in tumor cells was an independent adverse predictive factor for DFS and OS (P < 0.05).
  
  
  CONCLUSIONS
  The expressions of MIF and CXCR4 proteins in tumor cells and TILs have different clinically predictive values in ESCC.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Shu-Biao
authors.initials: SB
authors.lastname: Ye
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Tang
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.forename: Wan-Li
authors.initials: WL
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D015331:Cohort Studies; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007120:Immunochemistry; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012044:Regression Analysis; D016896:Treatment Outcome; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; D008263:Macrophage Migration-Inhibitory Factors; D019718:Receptors, CXCR4; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human