Investigation Of The Expression Of MTA1 Protein And Its Relationship To The Invasiveness, Metastasis And Prognosis In Esophageal Cancer

Background& Objective:Esophageal cancer is one of the most common malignancies treated by thoracic surgeons in China,the overall 5-year survival rate remains low.Most patients died of tumor invasiveness and metastasis,to search for the mechanisms of tumor invasiveness and metastasis has been an area of interest in oncology worldwide.With the further investigation of the cellular and molecular mechanisms of tumorigenesis,tumor invasiveness and metastasis,we learn more and more about the extremely complicated pathologic process about tumor invasiveness and metastasis.Many genes which are highly related to the tumor invasiveness and metastasis have been discovered and confirmed.These genes play an important role in the process of tumor invasiveness and metastasis,what's more,these genes and their corresponding products may become the therapy targets and the factors to estimate the prognosis and metastasis in patients with malignant tumors.MTA1(metastasisassociated gene 1)is one of the recently identified candidate metastasis-associated genes that plays an important role in tumorigenesis and tumor aggressiveness, especially tumor invasiveness and metastasis.Many studies support that MTA1 is associated with the invasiveness and metastatic potential of several human cancers (such as breast cancer,liver cancer and so on).However,there are only few reports about the expression of MTA1 protein in esophageal cancer.We performed this study with the aims to investigate the expression of MTA1 protein and its relationship to the invasiveness,metastasis and prognosis in esophageal cancer.Methods:56 esophageal squamous cell cancer tissues and 24 adjacent normal esophageal tissues were obtained from the patients who underwent complete resection via a right thoraco-abdominal approach(Ivor-Lewis esophagectomy)in Provincial Hospital Affiliated to Shandong University.All the 80 specimens were examined by immuno- histochemistry to detect the expression of MTA1 protein.All statistic analyses were performed with SPSS 10.0 statistical software.According to the clinicopathologic factors,the difference of MTA1 protein expression was compared by x~2 test.Kaplan-Meier method was performed to calculate the survival rate. Log-rank test was performed to compare the survival difference between the patients with and without MTA1 protein positive expression.Cox regression multivariate analysis was performed to determine independent prognostic factors.Results:Of all the 56 esophageal squamous cell cancer specimens,MTA1 protein was positive expression in 37(66.1%)specimens;MTA1 protein was negative expression in all the normal esophageal specimens;the difference of MTA1 protein expression between them was statistically significant(P＜0.001).The positive expression of MTA1 protein in patients with lymph node metastasis was significantly higher than those without metastasis(x~2=8.59,P＜0.05),and the MTA1 protein positive expression was also significantly associated with the weight loss(x~2=5.80, P＜0.05).However,no significant correlations with gender,age,length of tumor,histological differentiation and T stage were demonstrated for MTA1 protein positive expression.The overall 5-year survival rate was 30.4%;the 5-year survival rate in patients with MTA1 protein positive expression was significantly lower than those without MTA1 protein positive expression(13.5%vs 63.2%,P=0.0001).The results of multivariate analysis confirmed that T stage,lymph node metastasis and MTA1 protein positive expression were independent prognostic factors,respectively.Conclusions:MTA1 protein overexpression was detected in esophageal squamous cell cancer tissues and was found to be significantly associated with weight loss and lymph node metastasis.The results of multivariate analysis confirmed that T stage,lymph node metastasis and MTA1 protein positive expression were independent prognostic factors,respectively.MTA1 plays an important role in esophageal squamous cell cancer lymph node metastasis.Our findings suggest MTA1 as an accessory predictor of metastatic phenotype and a prognostic factor in esophageal squamous cell cancer.