Nuclear expression of glioma-associated oncogene homolog 1 and nuclear factor-κB is associated with a poor prognosis of pancreatic cancer

Oncology. 2013;85(2):86-94. doi: 10.1159/000353452. Epub 2013 Jul 16.

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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use
  • Carcinoma, Pancreatic Ductal / drug therapy
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Nucleus / metabolism*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Female
  • Gemcitabine
  • Hedgehog Proteins / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Transcription Factor RelA / metabolism*
  • Transcription Factors / metabolism*
  • Treatment Outcome
  • Zinc Finger Protein GLI1

Substances

  • Antimetabolites, Antineoplastic
  • GLI1 protein, human
  • Hedgehog Proteins
  • RELA protein, human
  • SHH protein, human
  • Transcription Factor RelA
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • Deoxycytidine
  • Gemcitabine