The Expression And Drug Resistance Research Of SUMO Specific Protease 1 In Non-small Cell Lung Cancer

Objective: 1.The aim of this study is to(1)investigate the expression of SUMO specific protease 1(SENP1)in non-small cell lung cancer tissues,(2)analyze the relationship between the SENP1 expression and clinic pathological features,(3)clarify the latent role of SENP1 in the pathogenesis and development of non-small cell lung cancer.2.The role of SENP1 in drug resistance is further analyzed by comparing SENP1 expression in non-small cell lung cancer cell line(A549)and platinum resistant tumor cell line(A549/DDP).Methods: 1.90 cases of non-small cell lung cancer tissues and paracancer tissues were collected from January 2014 to December 2015 in Department of thoracic surgery Qingdao Municipal Hospital,Immunohistochemistry was performed to detect the expression level and location of SENP1 protein.2.The expression level and location of SENP1 was analyzed in cultured A549 and A549/DDP cell line by immunohistochemistry and quantitative real-time PCR.3.The statistical software SPSS17.0 was used to analyze the data,P < 0.05 was considered to be statistically significant.Results: 1.SENP1 protein was located in cytoplasm and cell membrane in different types of non-small cell lung cancer.SENP1 expression in lung cancer tissues were significantly higher than paracancer tissues,the difference was statistically significant(P<0.05).SENP1 had different expression level in different histological types,Squamous carcinoma and adenocarcinoma had obvious difference in high expression group while total expression level was coincident(P<0.05).2.Immunohistochemistry staining results showed the location of SENP1 expression in lung adenocarcinoma was related to histological type.In micro papilla and solid adenocarcinoma,nuclear membranes were mostly stained.While in other types of adenocarcinoma,nuclear membranes staining were negative or with minute quantities,Significantly higher expression in nuclear membrane expression was observed in micro papilla and solid adenocarcinoma(P<0.05).3.The results showed SENP1 expression in lung cancer tissues was correlated to TNM stage(P<0.05),but was not correlated to the age,gender and smoking history(P > 0.05).4.The expression of SENP1 was mainly localized in cytoplasms in A549 and A549/DDP cell line.Partial cells of A549/DDP were also had nuclear membrane expression.Real-time PCR results showed that the expression of SENP1 m RNA in A549/DDP was significantly higher than A549 cell line(P<0.05).Conclusions: 1.Our results showed elevated expression of SENP1 protein in non-small cell lung cancer comparing to paracancer tissues.The expression level was obviously increased in high expression group in adenocarcinoma comparing to squamous cell carcinoma.SENP1 expression in lung cancer was related to TNM tumor stage.The results indicate SENP1 may be involved in the development of lung cancer through SUMO modification.The molecular mechanisms SENP1 promotes tumor progression may be variable in different histological type.SENP1 can be a candidate for indicating lung cancer prognosis.2.The expression location of SENP1 in adenocarcinoma lung cancer is related to tumor histological type.In solid and micro papillary adenocarcinoma with high incidentcy of invasion and metastasis,SENP1 had significantly increased expression on nuclear membrane.The results indicate that SENP1 may participate in tumor invasion and distant metastasis through nuclear / plasma shuttle.3.The increased expression of SENP1 in the platinum resistant tumor cells indicate that SENP1 may play a key role in drug resistance of non-small cell lung cancer through nuclear / plasma shuttle.It is expected to find new methods to resolve drug resistance in patients with non-small cell lung cancer.