Smo Expression At Diagnosis Predicts Prognosis In Resected Gastrointestinal Stromal Tumor Patients And Correlates To Imatinib-Resistance

Objective: The aim of this study was to investigate the prognostic value and role of imatinib-resistance due to the hedgehog signaling pathway in resected gastrointestinal stromal tumor (GIST) patients. Methods: The expression levels of Smoothened (Smo), Patched1 (Ptch1) and Gli1-3 were assessed in 12 resected GIST specimens by microarray, and were further verified in 24 Formalin-Fixed and Paraffin-Embedded (FFPE) tissues using RT-PCR. We also assessed the expression levels in 322 resected GIST specimens by using immunohistochemistry. The prognostic value of Smo, Ptch1 and Gli1-3 were investigated by overall survival (OS) and disease-free survival (DFS). The Smo, Ptch1 and Gli1-3 expression levels in GIST cells were evaluated in imatinib-resistant cell lines to verify their relationship with imatinib-resistance. Results: Higher expression levels of Ptch1 protein and lower expression levels Smo protein predict a better OS and DFS. Additionally, the Smo expression in imatinib-resistant cell lines was significantly higher than in imatinib-sensitive cell lines. The drug resistance decreased after interference of Smo in imatinib-resistant cell lines. Conclusions: Lower Smo expression and higher expression of Ptch1 at diagnosis predicts a better OS and DFS, and the high expression of Smo protein contributes to imatinib-resistance in GIST cells.