Association of the expression of the glioma-associated oncogene homolog (GLI) 1 with nuclear expression of NF-κB and unfavorable overall survival of patients with pancreatic cancer.

Abstract

4112 Background: Hedgehog signaling pathway is involved in the moleculopathogenesis of pancreatic cancer. In pancreatic cancer, NF-κB up-regulates sonic hedgehog (Shh) expression and further contributes to the activation of hedgehog (Hh) signaling pathway. In this study, we examined the association of Hh signaling pathway with NF-κB activation and clinical outcome of pancreatic cancer patients. Methods: We reviewed the medical records and pathologic specimens of 87 patients with histologically proven primary pancreatic cancer diagnosed at our institutions from January 1, 1995 through December 30, 2007. Of the pancreatic cancer patients, 74 with available tumor specimens for further evaluated for the expression of NF-κB (RelA/p65), sonic hedgehog (Shh), and Gli1 by immunohistochemistry. The expression of NF-κB activation and Hh signaling pathway correlated with the clinicopathologic features and overall survival (OS) of these patients. Results: The frequencies of expression of Shh, and nuclear expression of Gli1 and NF-κB were found in 68 (92%) of 74 cases, 29 (39%) of 74 cases, and 23 (31%) of 74 cases, respectively. The expression of Gli1 was closely associated with nuclear expression of NF-κB (P <0.001). Clinically, the initial stage (P = 0.006), the location of primary tumor (P = 0.001), and the response to chemotherapy (P = 0.003) were significantly associated with OS. Patients with nuclear expression of Gli1 had significant worse prognosis than those without (median survival [MS], 7.9 months versus 13.9 months, P = 0.009). Similarly, patients with nuclear expression of NF-κB had a shorter OS than those with negative or cytoplasmic expression of NF-κB (MS, 6.3 months versus 13.9 months, P <0.001). However, Shh expression lost of its prognostic significance of OS. 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 close interaction of Gli1 and NF-κB and its biologic significance may help us improve the treatment efficacy of this group of tumors.