Expression Of PTEN,p-mTOR,p-p70S6K And P-4EBP1 In Esophageal Oncogenesis And Its Relationship With Clinicopathological Parameters

Objective:1.To detect the protein expressions of PTEN,p-mTOR,p-p70S6 K and p-4EBP1 genes in esophageal squamous cell carcinoma(normal tissue low grade intraepithelial neoplasia high grade intraepithelial neoplasia squamous cell carcinoma).2.To analyze the correlation between the expression of the four gene proteins and the clinicopathological parameters in esophageal squamous cell carcinoma.Methods:1.Eighty-nine cases of esophageal squamous cell carcinoma and paracancerous tissues(34 cases of high-grade intraepithelial neoplasia,17 cases of low-grade intraepithelial neoplasia,and 59 cases of normal esophageal tissue)were collected to make tissue microarray.2.Immunohistochemical staining of PTEN,p-mTOR,p-4EBP1 and p-P70S6 K antibodies was performed to observe the protein expression levels of PTEN,p-mTOR,p-4EBP1 and p-P70S6 K in samples of each group.3.H-score was used to compare the differences in protein expression between the groups,and to analyze the correlation between the protein expression of each gene and the clinicopathological parameters of esophageal squamous cell carcinoma.Results:1.(1)The protein expression level of PTEN in normal esophageal tissues,low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and squamous cell carcinoma decreased gradually(the rate of H-score≥30 was 74.58%,58.82%,58.82%,19.10%);(2)The expression of p-mTOR protein was significantly higher in squamous cell carcinoma and high-grade intraepithelial neoplasia group(93.26%,100.00%)than in low-grade intraepithelial neoplasia group and normal group(70.59%,69.49%);(3)The expression level of p-p70S6 K in normal esophageal tissues,low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia increased gradually(32.20%,70.59%,85.29%),but decreased in squamous cell carcinoma(43.82%).(4)The protein expression of p-4EBP1 in normal esophageal tissues,low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and squamous cell carcinoma showed an increasing trend(22.03%,35.29%,55.88%,58.43%).2.The H-score of each gene protein in the normal group,low-grade neoplasia group,high-grade neoplasia group and squamous cell carcinoma group was:PTEN[60.00(20.00,80.00),60.00(7.50,80.00),55.00(5.00,105.00),0.00(0.00,15.00)];p-mTOR [110.00(30.00,140.00),170.00(60.00,240.00),285.00(200.00,296.25),240.00(150.00,292.50)];p-p70S6K[30.00(30.00,80.00),120(30.00,120.00),180(85.00,217.50),5.00(0.00,60.00)];p-4EBP1 [10.00(0.00,30.00),30.00(0.00,80.00),30.00(0.00,85.00),40.00(0.00,140.00)].The differences among the four groups were statistically significant(P<0.01),and the differences among the pairwise comparison groups were also statistically significant(P<0.05).3.In esophageal squamous cell carcinoma,the expression of PTEN protein was correlated with the depth of tumor invasion(P<0.05).The expression of p-mTOR protein was correlated with the clinical stage,pathological grade and invasion depth of tumor(P<0.05).The expression of p-p70S6 K protein was correlated with the clinical stage and invasion depth of tumor(P<0.05).4.The protein expression of p-p70S6 K and p-4EBP1 in esophageal squamous cell carcinoma was weakly and positively correlated(P<0.01),while the other factors were not correlated with each other(P>0.05).Conclusions:1.p-mTOR and p-4EBP1 gene proteins are highly expressed in esophageal squamous cell carcinoma,p-p70S6 K is an early event in the process of esophageal carcinogenesis,and PTEN is low expressed in esophageal squamous cell carcinoma.2.The protein expressions of PTEN,p-mTOR,p-p70S6 K and p-4EBP1 were significantly different in each stage of esophageal squamous carcinoma(P<0.05).3.PTEN,p-mTOR and p-p70S6 K were correlated with depth of invasion,pathological grade and clinical stage of esophageal squamous cell carcinoma.4.There was a weak positive correlation between p-p70S6 K and p-4EBP1 protein expression(P<0.05).