Comprehensive Analysis of the Role of Hedgehog Signaling and Prognostic Significance in Human Pancreatic Cancer

OBJECTIVE: To analyze the expression and mutation of Hedgehog (HH) signaling in pancreatic cancer patients in order to investigate the expression pattern, potential function, and prognostic significance of HH signaling in pancreatic cancer. STUDY DESIGN: In this study, we obtained the expression information of HH signaling of pancreatic cancer patients from Gene Expression Profiling Interactive Analysis (GEPIA) and cBioPortal databases. Then, bioinformation was analyzed for the prediction of association between HH signaling and pancreatic cancer, including co-expression analysis, enrichment analysis, and association analysis, etc. Kaplan-Meier plotter database was used to study the effect of HH signaling expression on survival of pancreatic cancer patients. RESULTS: The expression of HH signaling members SHH, SMO, GLI1, GLI2, and GLI3 in pancreatic cancer tissues were higher than those in normal pancreatic tissues. Co-expression analysis and enrichment analysis revealed that HH signaling was closely related to the fibrillar collagen family, which was an important reason for the massive proliferation of pancreatic cancer stroma. Meanwhile, the HH signaling crosstalk to multiple signaling to participate in the pathological process of tumor. Survival analysis showed that the expressions of PTCH1 and SMO in pancreatic cancer patients were associated with overall survival of pancreatic cancer, and the expressions of SMO, GLI1, GLI2, and GLI3 were associated with recurrence survival in pancreatic cancer. CONCLUSION: This study shows that HH signaling could be a promising target for pancreatic cancer therapy. PTCH1 and SMO could be used as early diagnostic markers for pancreatic cancer, and SMO, GLI1, GLI2, and GLI3 could be considered as markers for postoperative follow-up and detection of recurrence of pancreatic cancer.