Expression And Clinical Significances Of Hedgehog Signaling Pathway In Non-Hodgkin's Lymphoma

Objective The formation of Non-Hodgkin lymphoma (NHL) is composed of many steps and multistage process. Multiple genes and several cell signaling pathways may be involved, but the pathogenesis is still not clear. During recent years, abnormal activation of some signaling pathways as one reason of malignant tumors is generally accepted. Hedgehog (Hh) signaling pathway is involved in growth, apoptosis, transformation of tumor cells and new-vascularization. It makes new breakthroughs during studying of Hh pathway in the mechanism of tumor development. This pathway is extremely important in activation of tumors and malignant biological characteristics maintaining. Abnormal expression of Hh signaling pathway is also discovered in NHL, but little relevant reports. Therefore, we aim to discuss the expression and clinicopathologic significance of Gli1 and Gli2, two factors of Hh signaling pathway, in NHL.Methods 1. Gli1 and Gli2 mRNA of 18 NHL samples and 10 reactive lymphadenitises were amplified by Real-time PCR. We also analyzed the relationship between Gli1 and Gli2 mRNA levels and NHL clinical features.2. Gli1 and Gli2 protein of 25 NHL samples and 8 reactive lymphadenitises were assessed by immunohistochemical staining. The relationship between Glil and Gli2 protein levels and NHL clinical features was also analyzed.3. All the statistical analyses were carried out using SPSS 17.0. The significance of different groups were evaluated by medians and P<0.05 was considered statistically signigicant.Results 1. Glil and Gli2 mRNA of NHL group (RQ 2.05,2.31) were expressed higher than reactive lymphadenitis team (RQ 0.82,0.89). Glil mRNA activated level was positive related with Gli2 (r=0.63, P<0.01). In addition, Gli2 was also positively correlated to clinical stages of NHL (P=0.03)2. The positive expression rate of Glil and Gli2 were 80% and 68% respectively, which were extremely higher than reactive lymphadenitise tissues. Glil protein level was positive related with Gli2 (r=0.62, P <0.05).3. Both Glil and Gli2 protein expression were positively correlated to clinical stages of NHL (P=0.05, P=0.01). But the expressions of Gli1 and Gli2 mRNA had no significant correlation to B symptoms, bloodβ2-microglobulin, age and sex.Conclusion Glil and Gli2 were high expressed in NHL tissues, and closely related with clinical stages and prognosis of NHL. Further study in Hh signaling pathway will reveal the occurrence and development mechanism of NHL, which will bring breakthroughs in treatment of NHL.