title: Nuclear expression of glioma-associated oncogene homolog 1 and nuclear factor-κB is associated with a poor prognosis of pancreatic cancer.
abstract: OBJECTIVE
  We investigated the association of the hedgehog pathway with nuclear factor (NF)-κB and clinical outcomes in pancreatic cancer patients.
  
  
  METHODS
  We analyzed tissue samples for the expression of NF-κB (RelA/p65), sonic hedgehog (Shh) and glioma-associated oncogene homolog 1 (Gli1) by immunohistochemistry and investigated their expression in association with clinical outcomes.
  
  
  RESULTS
  Eighty-one patients with pancreatic cancer were investigated. Expression of Shh and nuclear expression of Gli1 and NF-κB were found in 63 of 66 (96%), 28 of 68 (41%) and 22 of 68 cases (32%), respectively. Nuclear Gli1 expression was closely associated with nuclear expression of NF-κB (p < 0.001). Patients with nuclear Gli1 had significantly worse prognoses than those without (median survival 7.9 vs. 13.9 months; p = 0.009). Similarly, patients with nuclear expression of NF-κB had shorter overall survival than those with negative or cytoplasmic expression of NF-κB (median survival 5.5 vs. 13.9 months; p < 0.001). Shh expression had no prognostic significance. In the multivariate analysis, NF-κB nuclear expression was closely associated with unfavorable overall survival (p = 0.02).
  
  
  CONCLUSIONS
  Our results indicate that nuclear expression of Gli1 or NF-κB is a strong predictor of poor prognosis in pancreatic cancer. Additional investigation of the biologic significance of this association is warranted.
authors.affiliation: Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Yang
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Lee
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Tien
authors.forename: Sung-Hsin
authors.initials: SH
authors.lastname: Kuo
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D051996:Transcription Factor RelA / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome; D000071676:Zinc Finger Protein GLI1; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C498143:RELA protein, human; C509239:SHH protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D003841:Deoxycytidine; D000093542:Gemcitabine