title: Stromal cell derived factor-1 and CXCR4 expression in colorectal cancer promote liver metastasis.
abstract: BACKGROUND
  Recent studies suggest that SDF-1 and CXCR4 are expressed in certain cancer cells, and malignant cells use this chemokine/receptor system to promote tumor progression and metastasis. However, the pathophysiological significance of their expression in colorectal cancer (CRC) tissue has not been fully elucidated.
  
  
  OBJECTIVE
  The purpose of this study was to assess SDF-1/CXCR4 expression and to explore its contribution to colorectal cancer.
  
  
  METHODS
  We examined SDF-1 and CXCR4 mRNA expression in 124 primary colorectal tumour and 35 liver metastases tissues and matched adjacent noncancerous tissues by reverse transcriptase PCR (RT-PCR). Furthermore, their expression was analyzed by immunohistochemistry. The relationship between SDF-1/CXCR4 expression and clinicopathological features were analyzed by appropriate statistics. X2 test and Kaplan-Meier analysis were used to investigate the correlation between the ligand-receptor expression and prognosis of colorectal cancer patients.
  
  
  RESULTS
  The relative mRNA expression of SDF-1 and CXCR4 was significantly elevated in colorectal cancer tissues as compared with adjacent noncancerous tissues (P < 0.001). The high expression of proteins expression in colorectal cancer tissues was significantly correlated with tumor grade (P = 0.0001), clinical stage (P < 0.05), and lymphatic invasion (P < 0.05). Furthermore, patients with CXCR4 nuclear-type expression showed more frequent lymph node metastasis (p = 0.021), advanced clinical stage (p = 0.001) and lymphatic invasion (p = 0.03) than those with cytoplasm staining-type. Kaplan-Meier survival analysis revealed that high expression of the couple SDF-1/CXCR4 correlated with poor prognosis of colorectal cancer patients (P < 0.001).
  
  
  CONCLUSIONS
  SDF-1 and CXCR4 may play an important role in the progression of colorectal cancer. The present data suggest that there is a significant association between SDF-1/CXCR4 to enhance the liver metastases causing poor prognosis. Those proteins may potentially be used as an independent biomarker for the prognostic evaluation of colon cancer in the Tunisian cohort.
authors.affiliation: Laboratory of Colorectal Cancer Research UR03ES04, Science University Tunis, Tunis, Tunisia.|Faculty of Sciences UTM, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Sameh
authors.initials: S
authors.lastname: Amara
authors.affiliation: Laboratory of Colorectal Cancer Research UR03ES04, Science University Tunis, Tunis, Tunisia.|Faculty of Sciences UTM, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Ines
authors.initials: I
authors.lastname: Chaar
authors.affiliation: Laboratory of Colorectal Cancer Research UR03ES04, Science University Tunis, Tunis, Tunisia.|Faculty of Sciences UTM, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Meriem
authors.initials: M
authors.lastname: Khiari
authors.affiliation: Laboratory of Colorectal Cancer Research UR03ES04, Science University Tunis, Tunis, Tunisia.|Faculty of Sciences UTM, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Donia
authors.initials: D
authors.lastname: Ounissi
authors.affiliation: Laboratory of Colorectal Cancer Research UR03ES04, Science University Tunis, Tunis, Tunisia.|Faculty of Sciences UTM, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Marwa
authors.initials: M
authors.lastname: Weslati
authors.affiliation: Laboratory of Colorectal Cancer Research UR03ES04, Science University Tunis, Tunis, Tunisia.|Faculty of Sciences UTM, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Rahma
authors.initials: R
authors.lastname: Boughriba
authors.affiliation: Department of Epidemiology and Preventive Medicine, Medicine University Tunis, Tunis, Tunisia.
authors.forename: Abdelmajid B
authors.initials: AB
authors.lastname: Hmida
authors.affiliation: Laboratory of Colorectal Cancer Research UR03ES04, Science University Tunis, Tunis, Tunisia.|Department of Pathology and Cytology, Mongi Slim Hospital, La Marsa, Tunis, Tunisia.|Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Saadia
authors.initials: S
authors.lastname: Bouraoui
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D012333:RNA, Messenger; D019718:Receptors, CXCR4
keywords: Colorectal cancer; chemokineschemokines receptor; liver metastases