Expression Of TGF ? R? Gene In Lung Adenocarcinoma With EML4-ALK Fusion Gene And Its Effect On The Biological Behavior Of Lung Adenocarcinoma Cells H3122

Background & Aims: At present,lung cancer is the first malignant tumor in the incidence and mortality rate in China.For the treatment of advanced non-small cell lung cancer(NSCLC),molecular targeted therapy has become a research hotspot,among which targeted therapy based on EML4-ALK fusion gene has attracted much attention.In addition,a number of scientists have found a new tumor suppressor gene TGF?RII.By verifying the expression level of TGF?RII in EML4-ALK fusion gene clinical lung adenocarcinoma samples,and the influence of TGF?RII on the invasion of lung adenocarcinoma H3122 cells,we could guide the clinical treatment of adenocarcinoma of lung with TGF?RII.Materials & methods: This study was divided into two parts.The first part was the clinicopathological study.We collected 484 cases paraffin embedded tumor tissue samples of lung adenocarcinoma patients underwent surgical excision who were from the First Affiliated Hospital of Guangzhou Medical University from December 2008 to December 2013.The EML4-ALK fusion genotyping of paraffin tissue samples from clinical patients with lung adenocarcinoma were identified by immunohistochemistry and real-time fluorescence quantitative method,the clinicopathological features of EML4-ALK positive lung adenocarcinoma at different stages was analyzed and the expression level of TGF?RII in clinical stage IA and IIIA EML4-ALK fusion gene positive samples.The second part is in vitro cell study.The experiment was divided into two groups,LV-shRNA-TGF?RII,and LV-shRNA-GP.After the stable expression of cell lines was constructed,Transwell was used to verify the effect of TGF-RII on the invasion of lung adenocarcinoma H3122 cells.We used SPSS 22.0for statistical analysis,single factor analysis of variance for result analysis,t-test for statistical treatment.When the P value less than 0.05,it was statistical significance.Results: The first part of the clinicopathological study: In 484 cases of lung adenocarcinoma,20 cases(5.85%)were positive for ALK expression,including 11 cases in IA stage and 9 cases in IIIA stage.The clinicopathological features of EML4-ALK fusion gene positive patients in stage IA and IIIA were analyzed,in IA and IIIA EML4-ALK positive patients,there were 5 and 6 cases of patients younger than 60 years old,6 and 3 in patients older than or equal to 60 years old,3 and 5 in smoking patients respectively.There were 8 and 4 cases in non smoking patients,and there was no difference in age and smoking(P>0.05).The results of RT-PCR detection showed that the relative expression of TGF beta R II mRNA in the EML4-ALK positive lung adenocarcinoma tissue of stage I A was significantly higher than that in the stage III A stage.The second part of in vitro cell study: After the successful construction of LV-shRNA-TGF beta RII/H3122 cell clones,the results showed that the silencing efficiency of TGF?RII was 85.97%.;The number of cells through transwell in the LV-shRNA-T?R II-H3122 cell group was more than that of the LV-shRNA-GP-H3122 cell group(P<0.05).Conclusion:The expression of TGF beta RII was significantly different in lung cancer tissues with positive EML4-ALK fusion gene at different stages.The expression level of TGF beta RII mRNA in EML4-ALK positive lung adenocarcinoma tissues was significantly lower than that in early tumor tissues.After silencing TGF beta R II gene,the invasiveness of ALK positive lung adenocarcinoma cells was significantly enhanced.