Correlation Study Between MICA/B And EGFR Gene,its Clinicopathological Features And Prognosis In Advanced Lung Adenocarcinoma

BackgroundLung adenocarcinoma researched by medical practitioners at home and abroad is a common cancer with poor prognosis,which is difficult to evaluate.Major histocompatibility complex class I chain-related protein A/B(MICA/B),as a tumor related antigen,has a close relationship with lung cancer Whether MICA/B can be used as a prognosis predictor for lung adenocarcinoma and the relationship between MICA/B and epidermal growth factor receptor(EGFR)gene,which is a driving gene of lung cancer,are unknown yet.ObjectiveStudy the relationship between EGFR gene and MICA/B expression in HCC827 cell of lung adenocarcinoma based on small interfering RNA(siRNA).Detect the expression of MICA/B in advanced lung adenocarcinoma and analysis its relationships with clinicopathological features and prognosis.MethodsLung adenocarcinoma HCC827 cells of logarithmic growth phase were divided into three groups randomly.EGFR-siRNA transfection group and siRNA control group were transfected with EGFR-siRNA specific transfection reagent and siRNA control reagent by liposome LipofectamineTM 2000 respectively,blank control group without transfection.In three groups,EGFR mRNA,EGFR protein and MICA/B were detected by reverse transcription polymerase chain reaction,Western blot and flow cytometry 48 hours after transfection.One hundred and twenty-six patients with advanced lung adenocarcinoma and intact archive wax block,who were admitted to the People’s Hospital of Zhengzhou fromJanuary 2008 to September 2010,were subject investigated.Those subjects enrolled were recorded in Excel regarding name,age,sex,TNM stage,T stage,histological grade,mutation status of EGFR gene,lymph node metastasis and the expression of MICA/B(Immunohistochemical staining,total staining score of high expression,low expression and negative expression was 0,1 to 2,≥3,respectively,non-high expression including negative and low expression)and survival etc,by a double recording,specially-assigned person check and timely backup way.The following up deadline was September 30,2015 and the data collected was analyzed by SPSS20.0.Result1.The differences of EGFR mRNA,EGFR protein and MICA/B among three groups was statistically significant(P<0.05),and EGFR-siRNA transfection group was lower than that of siRNA control group and blank control group(P<0.05).There were no statistical significance between siRNA control group and blank control group(P>0.05).1.5%agarose gel electrophoresis EGFR mRNA showed that optical density of siRNA control group and blank control group was similar,which was stronger than that of EGFR-siRNA transfection group.EGFR protein electrophoresis showed that EGFR protein bands was shallower of color and thinner of width than that of siRNA control group and blank control group.2.The high expression rate of MICA/B was 48.41%(61/126)for advanced lung adenocarcinoma tissues and MICA/B was expressed both cytoplasmic and membrane.3.The high expression rate of MICA/B was comparable among patients with different ages and genders(P>0.05)and differences were statistically significant in patients with different TNM stages,T stages,histological grade,lymph node metastasis,and mutation status of EGFR gene(P<0.05).The expression of MICA/B was negatively correlated with histological grade and positively correlated with T stage,TNM stage,mutation status of EGFR gene and lymph node metastasis(P<0.05).4.Single factor survival analysis showed that T stage,TNM stage,histological grade,mutation status of EGFR gene,lymph node metastasis,the expression of MICA/B were suspicious factors influencing the prognosis of advanced lung adenocarcinoma(P<0.05).Yet,ages and genders could not be regarded as the influencing factors(P>0.05).Multivariate survival analysis showed that mutation status of EGFR gene(HR=1.965,P=0.027)and expression intensity of MICA/B(HR=3.058,P=0.002)were independent influencing factors for patients with advanced lung adenocarcinoma(P<0.05).ConclusionMICA/B is associated with EGFR gene and the development of advanced lung adenocarcinoma.High expression of MICA/B and mutation of EGFR are independent risk factors for the prognosis of advanced lung adenocarcinoma.