Expression Of Hedgehog Pathway Gli Family Members In Nasopharyngeal Carcinoma And Their Clinical Significance

Objective: To study the expression pattern of Sonic Hedgehog signaling pathway nuclear transcription factor Gli1, Gli2, Gli3, and the expression of key factor PI3K/AKT signaling pathway,phosoho-AKT(P-AKT) in the nasopharyngeal carcinoma, and its potential clinical significance. Analyse the correlation of expression level of Gli1, Gli2, Gli3 and P-AKT, and explore the relationship between clinicopatholoncal factors and the expression of Gli1, Gli2, Gli3 and P-AKT. Method: The nasopharyngeal tissue samples(paraffin embedding tissue) of 60 cases were diagnosed by biopsy, and the clinical data of patients was completed. Moreover, alternative to fifteen paraffin-embedded human normal nasopharyngeal epithelial tissues samples obtained from Nanxishan Hospital of Guangxi Zhuang Autonomous Region, respectively, between June 2013 and June 2015. The protein expression level of Gli1, Gli2, Gli3 and P-AKT in nasopharyngeal carcinoma samples and human normal nasopharyngeal epithelial tissues samples were detected by immunohistochemistry staining. The result was gained according to the positive percentage and intensity of staining the degree of immunostaining. The percentage of positively stained cells was scored as follows: 0%- 5%(0), 6%- 25%(1), 26%- 50%(2), 51%- 75%(3), > 75%(4); the staining intensity was scored as follows:no staining(0), light yellow(1), yellowish brown(2), brown(3). The sum of the intensity and percentage scores was used as the Immuno-reactive-score(IRS). Sonic Hedgehog signaling pathway members Gli1, Gli2, Gli3 by IRS ≤ 6 were considered ‘low expression’, IRS ≥ 7 were considered ‘high expression’; IRS of P-AKT ≥ 4 as positive,IRS of P-AKT < 4 as negative. Using SPSS 18.0 Analysis Software,immune reaction between group of nasopharyngeal carcinoma and group of human normal nasopharyngeal epithelial tissues compared by application t test; the enumeration data was compared by χ2 test. The correlation between protein expression level by the Spearman rank correlation analysis, P < 0.05 was considered indicative of statistical siganificance, and the relationship between the expression of Gli1, Gli2, Gli3 and P-AKT, and the clinicopathological characteristics were analyzed. Result: Gli1, Gli2, Gli3, P-AKT were expressed at the cytoplasm and cell nucleus. Gli1, Gli2, Gli3 were expressed mainly in tumor cells, and subcellar location at the nucleus; P-AKT was expressed mainly in tumor cells,and subcellular location at the cytoplasm. The expression of Gli1, Gli2, Gli3, P-AKT in nasopharyngeal carcinoma were higher than human normal nasopharyngeal carcinoma(6.35±3.87 vs 2.73±2.02,P<0.001;5.70±4.13 vs 1.93±1.28,P<0.001;6.07±3.60 vs 3.27±2.55,P=0.004),P<0.05). The expression level of Gli1 and Gli2 were associated with lymph node metastasis(P<0.05); however,It wasn’t found that Gli3 protein associated to clinicopathological characteristics. The expression level of P-AKT was associated with lymph node metastasis(P<0.05), but wasn’t associated to other clinicopathological characteristics. Gli1 expression were correlated with Gli2, Gli3, P-AKT(r=0.380,P =0.003; r=0.313,P=0.015; r=0.284,P=0.028),respectively; Gli2 expression were correlated with Gli3 and P-AKT(r=0.609,P <0.001; r=0.416,P=0.001),respectively. Conclusion: It is demonstrated that Sonic Hedgehog Pathway nuclear transcription factor Gli( Gli1, Gli2, Gli3) and P-AKT were overepressed in nasopharyngeal carcinoma, and P-AKT expression were correlated with Gli1 and Gli2. It is suggested that PI3K/AKT signaling pathway is necessary for Hh Pathway implicated in development and promotion of nasopharyngeal carcinoma.