The Significance Of LIMD2 Expression In A Corhort Of Patients With Surgically Resected NSCLC

Objective:To explore LIMD2 expression and clinical significance in surgically resected NSCLC.Methods:We collected information of 141 NSCLC patients in Fuzhou general hospital from October 2010 to July 2014,25 cases of tissue adjacent to carcinoma were collected.For detecting tumor tissues in samples,the method of HE staining was used.We made use of AMRS and PCR methods to test the state of EGFR mutations in tumor tissues.The expression levels of LIMD2 and E-cadherin were investigated by IHC.The Immunohistochemical results of Ki-67 and VEGF that reported by our hospital were accepted.The chi-square test(2)was used to analyze associations between LIMD2 expression level and the different clinicopathological features.The DFS was analyzed by the Kaplan–Meier method,and the DFS difference between influence factors was assessed using the log-rank test.Correlation between LIMD2 and E-cadherin was tested by Spearman.Multivariate analyses for DFS were performed using the Cox proportional hazards model with a stepwise variable selection procedure.All tests were two-sided,and the statistical significance level was set at 0.05.Results:The median age of patients was 60 years old(range 27–80 years old).By the end of the last follow-up,105 patients occurred recurrence and 36 were free.The DFS ranges from 2.8-64.3m and the median DFS is 15.9m.96(68.1%)cases tumor differentiation were well or median,45(31.9%)cases were poor.Of the 141 patients,79(56.0%)had high Ki-67 expression level while 62(44.0%)had low level.74(52.5%)had high VEGF expression level,47(47.5%)had low level.43(30.5%)had EGFR mutation,98(69.5%)had wild type.Positive Ki-67 was more common in SCC(p=0.002)and poor tumor differentiation(P=0.000).Positive VEGF was more common in adenocarcinoma tumors(p=0.042).EGFR mutation was more common in female(P=0.023)and adenocarcinoma(P=0.000).Ki-67,VEGF expression level and EGFR mutation did not correlate with DFS.In the carcinoma tissue,71(50.4%)had high LIMD2 expression level,70(49.6%)had low level.In the tissue adjacent to carcinoma,7(28.0%)had high LIMD2 expression level,18(72.0%)had low level.LIMD2 expression level is different in the two kinds of tissue.In the carcinoma tissue,75(53.2%)had high E-cadherin expression level,66(46.8%)had low level.In the tissue adjacent to carcinoma,13(52.0%)had high E-cadherin expression level,12(48.0%)had low level.E-cadherin expression level is not different in the two kinds of tissue.LIMD2 expression correlated with the N stage,TNM stage and tumor differentiation.High LIMD2 expression level was more common in the shorter DFS patients(P=0.033).E-cadherin expression correlated with the T stage,N stage and TNM stage.High LIMD2 expression was related to low E-cadherin expression(R=-0.42,P = 0.000).High LIMD2 expression level was more common in the better DFS patients(P=0.000).Multivariate Cox regression analysis demonstrated that gender,T stage,TNM stage,tumor differentiation,LIMD2 and E-cadherin were related to DFS.Conclusion:LIMD2 may inhibit E-cadherin expression in NSLCL.The higher LIMD2 expression level in NSCLC tissue means shorter DFS after surgeon.LIMD2 may have a role in promoting NSCLC invasiveness and may be a promising independent biomarker for recurrence after surgeon.