The Expression Of MTA1 Protein In Stage â…  NSCLC And Its Effect On The Relapse, Metastasis And Prognosis

Background & Objective:Lung cancer is a malignant tumor which is most harmful to human health and life in nowdays world.Non-small cell lung cancer counts for 80%in total lung cancer.Lung cancer has the higher invasiveness and metastasis ability.The rates of recurrence and metastasis are high after operation so that lung cancer has a poor prognosis.Early discovery,diagnosis and treatment is beneficial to improving treatment effect and survival rate of lung cancer.StageⅠnon-small cell lung cancer is a special significance subgroup because its 5-year survival rate is best compare with other groups.There is a report that its 5-year survival rates is over 70%.It is regrettable that 30%～40%of the stageⅠnon-small-cell lung cancer(NSCLC) patients are subjected to recurrence and metastasis at last after the radical resection so as to reduce the survival rate.So the research of recurrence/metastasis mechanism and the search for markers reflecting recurrence/metastasis and prognosis of NSCLC is valuable in treatment and prognostic counseling.Many genes which are highly related to the tumor invasiveness/metastasis have been discovered and confirmed and have been the hot spot of tumour researches. MTA1(meastasis-associated gene 1) is one of the recently identified candidate metasis-associated genes that plays an important role in tumorigenesis and aggressiveness,especially invasion and metastasis.Many studies support that MTA1 is associated with the invasion 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 lung cancer especially stageⅠNSCLC.We performed this study with the aims to investigate the expression of MTA1 protein and its relationship to the recurrence,metastasis and prognosis of stageⅠNSCLC.Methods:All 60 stageⅠNSCLC tissues and 30 paracarcinous normal lung tissues were obtained from the patients who underwent radical resection and lymph nodes in Provincial Hospital Affiliated to Shandong University.All the 90 specimens were examined by immuno-histochemistry to detect the expression of MTA1 protein. All statistic analyses were performed with SPSS 13.0 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 60 stageⅠNSCLC specimens,MTA1 protein was positive expression in 22(36.7%) specimens while MTA1 protein was negative expression in all the paracarcinous normal lung specimens;the difference of MTA1 protein expression between them was statistically significant(P＜0.005).The positive expression of MTA1 protein in patients whose tumor diameter＞3cm was significantly higher than those≤3cm(x~2=6.33,P＜0.025),and the MTA1 protein positive expression was also significantly associated with the degree of tumor differentiation(x~2=7.89,P＜0.005).However,no significant correlations to age,gender,histopathological types and smoking status of lung cancer patients were demonstrated for MTA1 protein positive expression.Postoperative follow-up observed the frequency of recurrence/metastasis in stageⅠNSCLC patients with MTA1 protein positive expression(38.3%) was significantly higher than those negative expression.The overall 5-year survival rate of all the 60 stageⅠNSCLC patients was 68.3%;the 5-year survival rate in patients with MTA1 protein positive expression was significantly lower than those MTA1 protein negative expression (40.9%vs 84.1%,P=0.0001).The results of Cox's multivariate analysis confirmed that both MTA1 protein positive expression and the degree of lung cancer differentiation were independent prognostic factors,respectively.Conclusions:MTA1 protein overexpression was detected in stageⅠNSCLC tissues and was found to be significantly associated with tumor diameter and the degree of lung cancer differentiation.However,no significant correlations to age,gender,histopathological types and smoking status of lung cancer patients were demonstrated for MTA1 protein positive expression.The results of Cox's multivariate analysis confirmed that MTA1 protein positive expression and the degree of lung cancer differentiation were independent prognostic factors,respectively.MTA1 protein plays an important role in recurrence and metastasis of stageⅠNSCLC.The patient whose MTA1 protein was positive expression in tumor tissue had a bad prognostic.Our findings suggest MTA1 protein is an indicator for prognosis and evaluation of the recurrence and metastastic potential of operated patients with stageⅠNSCLC.