BACKGROUND: The sonic hedgehog (SHH) signaling pathway is critical in fetal organogenesis. Activation of the SHH pathway has been associated with several types of human cancer; however, the clinical impact of SHH activation in patients with gastric cancer is still unknown. METHODS: The present study included 41 patients with gastric cancer who underwent gastrectomy between 2000 and 2004. SHH, Patched-1 (PTCH1), Smoothened (SMO) and Glioma-associated oncogene-1 (GLI1) were examined immunohistochemically, and these of mRNAs from the cancer lesions were evaluated using real-time quantitative RT-PCR. RESULTS: Immunohistological expressions of SHH-related molecules were relatively intense in cancer tissue, but no significant correlation was found with any clinicopathological factors of tumor. PTCH1 was only the molecule associated with poor prognosis of patients with differentiated type of tumor. For mRNA analysis, a significant correlation was demonstrated between certain clinicopathological factors and PTCH1, SMO or/and GLI1 mRNA levels. High levels of SHH and PTCH1 mRNA were associated with poor prognosis. Multivariate analysis demonstrated the PTCH1 mRNA level and liver metastasis as significant independent prognostic factors. CONCLUSIONS: PTCH1 expression in the SHH pathway was possibly involved in gastric cancer tumor progression, and could be a useful indicator for the prognosis of gastric cancer.
BACKGROUND: The sonic hedgehog (SHH) signaling pathway is critical in fetal organogenesis. Activation of the SHH pathway has been associated with several types of humancancer; however, the clinical impact of SHH activation in patients with gastric cancer is still unknown. METHODS: The present study included 41 patients with gastric cancer who underwent gastrectomy between 2000 and 2004. SHH, Patched-1 (PTCH1), Smoothened (SMO) and Glioma-associated oncogene-1 (GLI1) were examined immunohistochemically, and these of mRNAs from the cancer lesions were evaluated using real-time quantitative RT-PCR. RESULTS: Immunohistological expressions of SHH-related molecules were relatively intense in cancer tissue, but no significant correlation was found with any clinicopathological factors of tumor. PTCH1 was only the molecule associated with poor prognosis of patients with differentiated type of tumor. For mRNA analysis, a significant correlation was demonstrated between certain clinicopathological factors and PTCH1, SMO or/and GLI1 mRNA levels. High levels of SHH and PTCH1 mRNA were associated with poor prognosis. Multivariate analysis demonstrated the PTCH1 mRNA level and liver metastasis as significant independent prognostic factors. CONCLUSIONS:PTCH1 expression in the SHH pathway was possibly involved in gastric cancer tumor progression, and could be a useful indicator for the prognosis of gastric cancer.
Authors: Monica D Nye; Luciana L Almada; Maite G Fernandez-Barrena; David L Marks; Sherine F Elsawa; Anne Vrabel; Ezequiel J Tolosa; Volker Ellenrieder; Martin E Fernandez-Zapico Journal: J Biol Chem Date: 2014-04-16 Impact factor: 5.157