title: CXCR4 Expression is Associated with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma.
abstract: BACKGROUND
  Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The chemokine CXCL12 and its receptors CXCR4 and CXCR7 were suggested to be involved in cancer invasion and metastasis. The aim of this retrospective study was to evaluate the prognostic impact of the expressions of CXCL12, CXCR4 and CXCR7 in patients with esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  We used immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate the expressions of CXCL12, CXCR4, and CXCR7 in ESCC patients' tumor biopsy specimens obtained during preoperative endoscopy or surgery. These results were compared with the patients' clinicopathological parameters and survival.
  
  
  RESULTS
  IHC was conducted for 172 patients. High expression of CXCR4 in the cytoplasm and nuclei and that of CXCR7 were associated with poor cause-specific survival (CSS) (P= .002 and .010, respectively). The specimens from 52 of the 172 patients were examined by RT-PCR and quantitative real-time PCR. The expression levels of messenger RNA (mRNA) of CXCR4 and CXCR7 were significantly increased in the tumors compared with normal esophageal mucosae (P < .0001). The expression level of mRNA of CXCR4 was associated with poor recurrence-free survival and CSS (P = .012 and .038, respectively).
  
  
  CONCLUSIONS
  CXCR4 expression is associated with poor prognosis in patients with ESCC.
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan. tyoshida1@tokushima-u.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Sainokuni Higashiomiya Medical Center, Saitama, Japan.
authors.forename: Yota
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Kochi Health Sciences Center, Kochi, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Furukita
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Kochi Health Sciences Center, Kochi, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kawakita
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishino
authors.affiliation: Shikoku Medical Center for Children and Adults, Kagawa, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Minato
authors.affiliation: Tokushima Red Cross Hospital, Tokushima, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yuasa
authors.affiliation: Kochi Red Cross Hospital, Kochi, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yamai
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takechi
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Seike
authors.affiliation: Department of Molecular and Environmental Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Bando
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tangoku
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D016629:Esophagectomy; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C501896:ACKR3 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D012333:RNA, Messenger; D054387:Receptors, CXCR; D019718:Receptors, CXCR4