Publications (2)2.46 Total impact
-
Article: The Hedgehog signalling pathway and its prognostic impact in human gliomas.
[show abstract] [hide abstract]
ABSTRACT: 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. 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. 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. 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.ANZ Journal of Surgery 06/2011; 81(6):440-5. · 1.25 Impact Factor -
Article: Upregulation of matrix metalloproteinase-1 and proteinase-activated receptor-1 promotes the progression of human gliomas.
[show abstract] [hide abstract]
ABSTRACT: Matrix metalloproteinases (MMPs) have been proposed to be involved in remodeling the tumor-stromal microenvironment. The protease-activated receptors (PARs) are the latest MMP targets. Recent studies have revealed that stromal-derived MMP-1 acts as a signaling molecule by cleaving PAR1 to cause tumor migration and invasion of various cancers. However, the involvement of MMP-1/PAR1 signaling pathway in the progression and prognosis of human gliomas remains to be identified. Immunohistochemical staining was performed to detect the expression patterns of MMP-1 and PAR1 in biopsies from 108 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyzes were performed to evaluate the prognosis of patients. Immunostaining revealed MMP-1 to be expressed in 83.3% (90/108) and PAR1 in 76.9% (83/108) of the biopsies. PAR1 expression was significantly correlated with that of MMP-1 (r = 0.786, p<0.0001). The total IHC scores for MMP-1 and PAR1 were significantly higher in high-grade tumors than in low-grade tumors (both p = 0.001). In addition, patients with high MMP-1 and high PAR1 expression have lower Karnofsky performance scale (KPS) scores than patients with low MMP-1 and low PAR1 expression (both p = 0.008). Moreover, MMP-1 and PAR1 expression was shown to be a strong prognostic marker for decreased overall survival (p = 0.002 and 0.003, respectively). Furthermore, Cox multi-factor analysis showed that KPS (p = 0.008), WHO grade (p = 0.006), MMP-1 (p = 0.006), and PAR1 (p = 0.008) were independent prognostic factors for human gliomas. Our results suggest that in gliomas, the upregulation of MMP-1 and PAR1 correlates with histological malignancy grade and clinical outcome. Also, MMP-1 and PAR1 immunostaining supplements the current histological grading by offering additional prognostic and predictive information.Pathology - Research and Practice 11/2010; 207(1):24-9. · 1.21 Impact Factor
