Expression Of PTPN12 In Esophageal Squamous Cell Carcinoma And Their Clinical Implications

Objective: There is very few report studying the relationship between PTPN 12 and esophageal squamous cell carcinoma patients in China.This study is to investigate PTPN12(Protein Tyrosine Phosphatase,Non-Receptor Type 12)expressions in human ESCC(esophageal squamous cell carcinoma)tissues and to explore the relationship between PTPN12 expressions and clinicopathological features of human ESCC.And to evaluate the influence of PTPN12 expression level in the postoperatives with ESCC.Methods:1 200 cases of ESCC and 41 cases of normal esophageal mucosa and 41 cases of ESCC adjacent tissues were collected form Hebei Medical University Fourth Hospital between 2004 and 2016.Immunohistoehemistry on TMAs was performed to measure the expression of PTPN12,the expression of PTPN12 in esophageal squamous cell carcinoma were analysed.2 Clinicopathologic characteristics of 200 patients,including age,gender,TNM stage,lymph node status were recorded.The correlations between PTPN12 expression and clinicopathologic characteristics were analyzed.3 To analyze the effect of PTPN12 protein expression on the prognosis of patients with esophageal squamous cell carcinoma.4 The expression of PTPN12 protein in 41 cases of ESCC,ESCC adjacent tissues and normal esophageal mucosa was analyzed test.The relationship between the PTPN12 expression and the clinical parameters of esophageal squamous cell carcinoma was analyzed by X2 test.The analysis of the distribution of PTPN12 in both OS and TTR of the postoperatives with ESCC was performed by Kaplan-Meier and Cox Regression method.Results:1 The results of the immunohistoehemistry showed that low-expression of PTPN12 was located in the cytoplasm and cell membrane of human ESCC.And PTPN12 expression was significantly lower in ESCC tissue than normal esophageal mucosa(P=0.01).These results suggest that PTPN12 is a low expression state and that PTPN12 may be a tumor suppressor gene in esophageal squamous cell carcinoma.There was no obvious difference between ESCC tissue and ESCC adjacent tissues(P=0.054),normal esophageal mucosa and ESCC adjacent tissues(P=0.091)in the expressions of PTPN12.2 Expression of PTPN12 in ESCC tissue was closely related with lymphatic metastases(P=0.034<0.05),TNM stage(P=0.018),Invasion depth(P=0.027),Tumor size(P=0.035),History of drinking(P=0.020),but had no relationship with age,gender,History of smoking and family history of cancer.3 Univariate analysis was calculated by the Kaplan-Meier method(the log-rank test).Then,the results showed that low-expression of PTPN12 in tumor,lymphatic metastases,TNM stage,Invasion depth,Tumor differentiation,were the risk factors that affect the survival of the postoperatives with ESCC.And low-expression of PTPN12 in tumor,lymphatic metastases,TNM stage,Invasion depth,Tumor differentiation were the risk factors of the recurrence.The survival of the over-expression of PTPN12 group was significantly higher than the lower expression group(P=0.006<0.05),and the TTR was obvious lower than the the lower expression group(P=0.003<0.05).4 Multivariate analysis was done using the Cox multivariate Proportional hazards regression model with stepwise manner(forward,likelihood ratio).The low-expression of PTPN12 in ESCC tissue was an independent risk predictive indicator for survival(HR=1.478,95%CI for Exp(B):0.975-2.241,P=0.048)and recurrence(HR=1.691,95% CI for Exp(B):1.018-2.808,P=0.043).lymphatic metastases(HR=0.483,95% CI for Exp(B):0.274-0.852,P=0.012),Poor tumor differentiation(HR=0.568,95%CI for Exp(B):0.349-0.924,P=0.023)and without reasonable postoperative adjuvant chemotherapy(HR=2.077,95%CI for Exp(B):1.420-3.037,P=0.000)were an independent risk predictiveindicator for survival.Conclusions:1 The results of PTPN12 expression was significantly lower in ESCC tissue than normal esophageal mucosa.These results suggest that PTPN12 is a low expression state and that PTPN12 may be a tumor suppressor gene in esophageal squamous cell carcinoma.2 The expression of PTPN12 in ESCC tissue was closely related with lymphatic metastases,TNM stage,Tumor size,Invasion depth and History of drinking showed that PTPN12 may be involved in the occurrence,invasion and metastasis of esophageal squamous cell carcinoma.3 The low-expression of PTPN12 in ESCC cells was an independent risk factor for postoperative recurrence and survival,and may serve as an important role in the metastasis and recurrence ESCC cells.The survival of the over-expression of PTPN12 group was significantly higher than the the lower expression group,and the TTR was obvious lower than the the lower expression group.These results suggest that the high expression of PTPN12 protein may play an important role in inhibiting the metastasis and recurrence of esophageal squamous cell carcinoma.Therefore,PTPN12 may be used as an indicator to predict the prognosis of patients with esophageal squamous cell carcinoma,and provide some new ideas for the molecular targeted therapy of esophageal squamous cell carcinoma.4 Lymphatic metastases and without reasonable postoperative adjuvant chemotherapy were independent risk predictive indicator for survival and recurrence.