Identification of signature genes for detecting hedgehog signaling activation in gastric cancer.

The aim of this study was to investigate the expression of hedgehog signaling molecules in gastric cancer. In situ hybridization, immunohistochemistry and RT-PCR for hedgehog signaling molecules, smoothened (SMO), suppressor of fused [Su(Fu)], and the target genes hedgehog-interacting protein (HIP) and platelet-derived growth factor receptor α (PDGFRα) were performed in 30 gastric cancer and two gastritis specimens. Using in situ hybridization, SMO expression was detected in 18/30 cancerous specimens (60%) as well as in 1/2 gastritis specimens (50%). Su(Fu) was expressed in 15/30 (50%), HIP in 14/30 (≈47%), and PDGFRα in 6/30 (20%) gastric cancer specimens. Despite the heterogeneous expression pattern, SMO, Su(Fu) and PDGFRα transcripts were highly correlated with the HIP transcript in the 30 gastric cancer specimens (p=0.0006, 0.0003 and 0.0441, respectively). Results from the in situ hybridization were further confirmed by RT-PCR for the expression of all of the genes and by immunohistochemistry for SMO expression. The findings revealed a set of genes for detecting Hh signaling activation in gastric cancer.