Investigations On The Roles Of Hedgehog Pathway In Prostate Cacer

Objective:Hedgehog(Hh)signaling pathway is initiated by the secreted Hedgehog proteins.It plays an essential role in embryogenesis and differentiation.Mutations in hedgehog signaling pathway genes,especially Patched (Ptch)and Smoothened(Smo)lead to over-expression of GLI-1 and other hedgehog target genes,resulting in various phenotypes,including medullobalstoma, Rubinstein-Taybi syndrome,small cell lung cancer,nevoid basal cell carcinoma syndrome,basal cell carcinoma,etc.The important role of Hedgehog signaling in the occurrence,progression in prostate is well established,however,it is not certain that Hedgehog signaling plays an important role in prostate cacer.Our study aimed at investigating the expression of the Shh,Ptch-1 and Gli-1 of Hedgehog signaling pathway in prostatic carcinoma tissues tissues and paracarcinoma tissues.To explore the role Shh,Ptch-1 and Gli-1 played in the oncogenesis,development, metastasis of human prostatic carcinoma.To determine the relationship between Shh,Ptch-1 and Gli-1 expression and the clinic and pathological features of human prostatic carcinoma.Method:The expression of Shh,Ptch1 and Gli1 was detected in prostatic carcinoma tissues and paracarcinoma tissues using immunohistochemistry.The Shh,Ptch1 and Gli1 expression was compared in different tissues.The relationship between ther expression and related clinic and pathological features(include:body weight, preoperative prostate-specific antigen level,preoperative prostate weight calculated by B-us, clinical stage,gleason level and prognosis etc.)was statistically analyzed. Results:1.The positive expression rate of Shh,Ptch1 and Gli1 protein was 94% (48/51),98%(50/51)and 100%(51/51)respectively detected by immunohistochemistry.The content of Shh,Ptch1 and Gli1 in Pca was markedly elevated compare with their corresponding adjacent normal tissues at protein level (P＜0.01).2.The expression of Shh,Ptch1 and Gli1 in 51 Pca cases have no relationship with body weight,preoperative prostate-specific antigen level,preoperative prostate weight calculated by B-us and prognosis(P＞0.05);The expression of Shh,Gli1 was associated with pathological grade(Gleason level)as well as clinical stage(P＜0.05),more advanced clinical stage and lower Gleason level cause more strong the expression.But the expression of Ptch1 have no relationship with them.3.The expression of Shh,Ptch1 and Gli1 in 51 Pca cases present some relationship with each other,but only between Shh and Ptch1 have positive correlation and this correlation has statistical significance(P＜0.05),more Shh expression more Ptch1 expression.4.The preoperative prostate-specific antigen level in 51 Pca cases have no relationship with body weight,Preoperative prostate weight calculated by B-us,prognosis as well as pathological grade(Gleason level)(P＞0.05);but have relationship with clinical stage(P＜0.05),the level in C+D stage was higher than that in A+B stage.Conclusion:1.The elevated expression of Shh,Ptch1 and Gli1 strongly activate the hedgehog signaling pathway in Pca.The activation of hedgehog signaling pathway associate with clinical stage and Gleason level.2.Gli1 has potential to be a better diagonostic marker for prostate cancer than Shh. Gli1 is related to the grade of prostate cancer,it can predict the degree of differentiation and the level of cell proliferation in prostate cancer.3.As the components of Hh signaling pathway,Shh,Gli1 may be ideal targets for the diagnosis and therapy of Pca.