title: CXCR4 expression predicts early liver recurrence and poor survival after resection of pancreatic adenocarcinoma.
abstract: OBJECTIVE
  Liver metastasis develops in 60% of patients after resection of pancreatic adenocarcinoma (PAC) and carries a dismal prognosis, but factors predictive of liver recurrence are poorly understood. Experimental evidence suggests that liver metastasis of PAC is mediated by CXCL12/CXCR4 signaling and can be inhibited by CXCR4 antagonist. We aimed to verify whether CXCR4 expression predicts early liver recurrence and poor survival after resection, and to explore the usefulness of CXCR4 status for prognosis prediction.
  
  
  METHODS
  Ninety-seven consecutive PAC patients undergoing R0 resection were analyzed. CXCR4 expression was analyzed by immunohistochemistry, and its associations with liver recurrence-free survival and overall survival were analyzed by Kaplan-Meier estimates and multivariable Cox and accelerated failure time regression models.
  
  
  RESULTS
  CXCR4-positive patients had a worse prognosis than CXCR4-negative patients, with a shorter liver recurrence-free survival (median: 8.7 vs. 39.7 months; P=0.004) and overall survival (median: 10.2 vs. 22.3 months; P<0.001). Overall survival for CXCR4-positive stage IIa patients was similar to that for stage IIb patients and significantly shorter than that for CXCR4-negative stage IIa patients (median: 9.7 vs. 27.4 months; P=0.002). CXCR4 positivity was significantly associated with liver recurrence (adjusted hazard ratio 2.22, 95% confidence interval (CI) 1.15-4.30; P=0.018) and predicted a 46% (95% CI 9-68%) and 35% (95% CI 7-54%) reduction in liver recurrence-free survival and overall survival, respectively.
  
  
  CONCLUSIONS
  Tumor CXCR4 expression independently predicts early liver recurrence and poor overall survival after resection of PAC. CXCR4 status stratifies stage IIa patients into two groups with a striking difference in prognosis.
authors.affiliation: 1] Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan [2] Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Liao
authors.forename: Hsiu-Po
authors.initials: HP
authors.lastname: Wang
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Huang
authors.forename: Ming-Shiang
authors.initials: MS
authors.lastname: Wu
authors.forename: Hung
authors.initials: H
authors.lastname: Chiang
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Tien
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Lin
authors.forename: Jaw-Town
authors.initials: JT
authors.lastname: Lin