PTCH1, a receptor of Hedgehog signaling pathway, is correlated with metastatic potential of colorectal cancer.

摘要

BACKGROUND: Approximately 90% of colorectal cancer (CRC) deaths arise from the metastatic dissemination of primary tumors. It is difficult to predict metastasis of colorectal cancer, especially for patients with the same pathological subtype and differentiation. AIMS. To identify biomarkers for predicting CRC metastasis. PATIENTS AND METHODS: We collected 19 primary tumors of CRC with identical pathological subtype, differentiation, and comparable Dukes' stages from patients with matched age and gender but completely different prognosis. Patients were divided into one high-risk and one low-risk group for metastasis. The expression levels of SHH, PTCH1, and sFRP1, which are components of the Hedgehog signaling pathway, were determined by real-time reverse transcription polymerase chain reaction (RT-PCR). To investigate further the correlation between expression level of PTCH1 and metastatic potential of CRC cells, we compared the mRNA and protein levels of the PTCH1 gene in LoVo cells with high metastatic potential and in HT-29, SW480, and SW620 cells with low metastatic potential by RT-PCR and flow cytometry. RESULTS: We found that tumor tissues in the high-risk group for metastasis expressed lower levels of PTCH1 mRNA than did those in the low-risk group. Similarly, mRNA and protein levels of PTCH1 were inversely correlated with the metastatic potential of CRC cell lines. Expression levels of SHH and sFRP1 genes did not differ between the two groups. CONCLUSION: Our data suggest that PTCH1 might be a potential biomarker that could discriminate CRC with high from that with low metastatic risk.