Hedgehog Signaling Pathway Proteins in Prognosis of Pancreatic Ductal Adenocarcinoma and Its Differentiation From Chronic Pancreatitis

Objectives The Hedgehog signaling pathway (Hh) probably plays a role in development and progression of pancreatic ductal adenocarcinoma (PDAC). Methods In our study, 114 patients (83 with PDAC and 31 with chronic pancreatitis [CP]) after pancreatic surgery were enrolled. The immunoexpression of Sonic hedgehog (Shh), Smoothened (Smo), and Glioblastoma transcription factor 1 (Gli1) and Ki-67 were detected in tissue specimens. Results Mean (standard deviation) immunoexpression of all Hh pathway molecules was significantly higher in PDAC than in CP patients: Shh, 2.24 (0.57) versus 1.17 (0.25) (P < 0.01); Smo, 2.62 (0.34) versus 1.21 (0.23) (P < 0.01); and Gli1, 1.74 (0.74) versus 1.15 (0.72) (P < 0.01). Patients with a lower expression level (z score <0) of Shh and Ki-67 have longer overall survival when compared with z score >0 (15.97 vs 8.53 months [P = 0.0087] and 15.20 vs 5.53 months [P = 0.0004], respectively). In addition, Shh sensitivity in PDAC detection was 84.3%; specificity, 93.5%; positive predictive value, 97.2%; and negative predictive value, 69%. Conclusions Our results suggest the prognostic role of the Hh pathway in PDAC and a role in the differential diagnosis with CP.