The Hedgehog signalling pathway and its prognostic impact in human gliomas

Objective: Aberrant activation of Hedgehog signalling pathway is involved in the progression of various human tumours, such as gastric cancer, paediatric brain tumour and hepatocellular carcinoma. However, the correlation of this signalling with tumourigenesis and patients' survival of gliomas has not been well documented. The present study was undertaken to examine the expression of Hedgehog signalling pathway in gliomas to elucidate its prognostic value in this tumour. Methods: Surgical specimens were obtained from 118 patients with primary gliomas. The expression of sonic hedgehog (Shh), its receptor patched (Ptch), and downstream transcription factor Gli1 was evaluated using immunohistochemical staining. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Results: Immunostaining revealed that the activation of Hedgehog signalling pathway was significantly associated with the Karnofsky performance scale (KPS) score and World Health Organization (WHO) grade of patients with gliomas. Especially, the positive expression rates of Shh, Ptch and Gli1 were significantly higher in patients with higher grade (P = 0.008, 0.008 and 0.01) and lower KPS score (P = 0.009, 0.009 and 0.02). Statistical analysis showed that patients expressing Shh, Ptch and Gli1 have poorer overall survival rates than those not expressing these proteins. Cox multi-factor analysis showed that KPS (P = 0.02), WHO grade (P = 0.008), Shh (P = 0.01), Ptch (P = 0.01) and Gli1 (P = 0.03) were independent prognosis factors for human gliomas. Conclusion: These results provide convincing evidence that the Shh-Ptch1-Gli1 signalling pathway is activated in human gliomas and correlates with clinicopathologic features as well as with prognostic parameters of the tumours. Hedgehog signalling pathway may therefore play an important role in the malignant potential and survival of gliomas.