Expressions And Significances Of Smo And Gli1 In Esophageal Squamous Cell Carcinoma

Background and objectiveEsophageal cancer is one of the most common malignancies, and about 30 million people around the world die of it each year. China is the high-risk area of esophageal cancer, and the mortality is the fist in the whole nation. Its pathogens is yet unknown. Sonic hedog hog (Shh) is one of major signaling pathways in human embryo development, which regulate cell proliferation and tissue differentiation a large amount of researches have proved that multiple cancers are closely associated to Sonic hedgehog signaling pathway abnormalities. It has been found the mutation or abnormal expression of key members of Sonic hedgehog signaling pathway in human basal cell carcinoma, Exogenous Shh can promote the proliferation of colorectal mucosa cells and cancer cells. Sonic hedgehog signaling pathway,particularly Smo protein witll activation function. Smo proteins in tumors, infiltration, transfer, etc in the process to have the vital significance.Recently, it has been found that many signaling pathways regulate process of embryo development and tissue differentiation largely affect processes of tumourigenesis, such as shh signaling pathway, EGFR signaling pathway, Notch signaling pathway, Wnt signaling pathway. The viewpoint that the signaling pathway controlling embryo development of vertebrates may be concerned with human tumourigenesis supplies new research directions of tumourigenesis mechanism.Sonic hedgehog signaling pathway is comprised by secretory sonic hedgehog-glycoprotein (shh) ligand,t ransmembrance protein receptor patched(Ptc), transmembrance protein smoothened (Smo) and downstream transcription Gli protion (Glil, Gli2, Gli3). In no circumstances Shh ligands Ptch suppressed across a cell membrane receptor another transmembrane receptor activity of Smo protein, resulting in pathways Shh, and deactivation in combination with Ptch, lifting the Ptch Smo inhibition of Smo, Ptch as inhibiting factor, and Glil is taken as a transcription effect factors. The occurrence of esophageal squamous cell carcinoma in Sonic hedgehog in the process of signaling pathways, abnormal activation may through high Smo protein over-active downstream transcription factors Glil protein expression of part of the occurrence of esophageal cancer.Presently there is no study on the expression of Smo in esophageal squamous cell carcinoma (ESCC). In order to discuss the correlation of genes of Smo and Glil with growth and trans-infiltration of (ESCC), find the targets of early detecting ESCC growth and metabasis, we detect mRNA and protein expression levels of Smo and Glil in ESCC by in situ hybridization and immunohistochemical staining, analysis the relationship between Smo and Glil and between them and invasion and metastasis of ESCC.Material and method1. The immunohistochemical staining was used to measure the protein expression of Smo and Glil in 68 cases of ESCC,68 cases of normal esophageal mucosa and 35 cases of adjacent atypical hyperplasia tissues.2. In situ hybridization was used to detect the used to detect the mRNA expression of Smo and Glill in 68 cases of ESCC,68 cases of normal esophageal mucosa and 35cases of adjacent atypical hyperplasia tissues.3. Statistical analysis was carried out using Statistical Package for Social Sciences (SPSS) P, version 13.0 for windows. Chi-square test, one-way analysis of variances and two independent-samples t test were used. P-values of P<0.05 were considered to be statistically significant.Result1.The positive rates of Smo protein (69.1%) and mRNA (63.2%) in ESCC were significantly higher than in adjacent atypical hyperplasia (28.6%,14.3%) and in normal esophageal mucosa(0%,0%).There were significant differences in the expressions of Smo among the three groups(P<0.05).2.The positive rates of Smo protein (79.4%) and Glil mRNA (79.4%) with tumor invaded into fiber membrane were significantly higher than those with tumor invaded into deep muscle layer (68.0%,60.0%) and tumor invaded into shallow muscle layer (33.3%,11.1%). The differences among the three groups ere statistically significant (P<0.05).3. With the increase of histological grade, Smo mRNA (100%,69.2% and 5.5%) and protein (87.5% for 69.2%, and 44.4%) expression was signi fficant change. There were significant differences among different groups (P<0.05).4. The positive rate of Smo protein (60.4%) and Smo mRNA (54.2%) without lymph node metastasis were significantly lower than those with lymph node metastasis (90%,85%). The difference between the two groups was statistically significant (P<0.05)5. The positive rates of Glil mRNA (70.6%) and protein (73.5%) in ESCC were significantly higher than in adjacent atypical hyperplasia (17.1%,34.3%) and in normal esophageal mucosa (2.60%,2.60%). There were significant differences in the expression Of Glil among the three group (P<0.05).6.The positive rates of Glil mRNA (82.4%) and protein (82.4%) with tumor invaded into fiber membrane were significantly higher than those with tumor invaded into deep muscle layer (72.0%,76.0%) and tumor invaded into shallow muscle layer (22.2%,33.3%). The difference between the two groups was statistically significant (P<0.05)7. With the increase of histological grade, Glil mRNA 11.1%,84.5% and 100% and protein44.4%,76.9%,91.7% expression was significant changed. There were no significant differences among different groups (P<0.05). 8.The positive rate of Glil mRNA (62.5%) and protein (66.7%) without lymph node metastasis were significantly higher than those with lymph node metastasis (90% and 90%),The difference between the two groups was statistically significant (P<0.05).9. There was a positive correlation between the mRNA and protein expressions of Smo and Glil in ESCC. (P<0.05)Conclusion1. Smo and Glil may play an important role in the process of invasion and metastasis of ESCC.2. Smo and Glil protein expressions are positively correlated, suggesting that Abnormal expression of Smo has a certain synergy in the development of ESCC by adjusting Glil's expression.