Studies On Macrophages And Angiogenesis Related Proteins In Lung Adenocarcinoma Tumor Microenvironment

Objective:1、To study the expression of macrophage-associated proteins(CD68,HLA-DR,CD163)and angiogenic-associated proteins(e NOS)during the occurrence and development of lung adenocarcinoma(normal tissue → pre-invasive lesion → invasive adenocarcinoma),analyze the infiltration of tumor-associated macrophages,and search for evidence of changes in tumor microenvironment during the occurrence of lung adenocarcinoma.To provide theoretical basis for pathological diagnosis of lung adenocarcinoma.2、The correlation of protein expression in lung adenocarcinoma microenvironment and its relationship with clinicopathological parameters were analyzed to further explore the influence of protein expression status on the prognosis of patients.Methods:1、A total of 144 cases of lung adenocarcinoma were selected and divided into three groups according to the lesion type: 96 cases of invasive adenocarcinoma,48 cases of pre-invasive lesion(AIS+AAH),and 48 cases of paracarcinoma normal lung tissue.2、Making tissue chips for invasive adenocarcinoma: Due to the heterogeneity of the tumor,in order to improve the accuracy,two points in different areas of each sample were taken to make tissue chips.3、The expression of macrophage associated proteins(CD68,HLA-DR,CD163)and vascular endothelial associated proteins(e NOS)in the interstitium of each group were detected by immunohistochemical method,and the protein expression levels of each group were observed.4、The differences in protein expression between groups were compared,and the correlation between protein expression and clinicopathologic parameters of lung invasive adenocarcinoma was analyzed.Results:1、(1)The expressions of CD68 and HLA-DR proteins in invasive adenocarcinoma and preinvasive lesions were significantly higher than those in normal lung tissue,and their expressions were the highest in preinvasive lesions;(2)The expressions of CD163 and e NOS protein increased during the progression of lung adenocarcinoma.2、The expression of each protein in the group was correlated:(1)In normal lung tissue,CD68 was positively correlated with HLA-DR protein expression(P=0.014,r=0.353);(2)In preinvasive lesions,CD68 was positively correlated with HLA-DR protein expression(P=0.002,r=0.444),CD68 was positively correlated with CD163 protein expression(P=0.021,r=0.333);(3)In invasive adenocarcinoma,CD68 was positively correlated with HLA-DR protein expression(P<0.001,r=0.476),and CD68 was positively correlated with CD163 protein expression(P<0.001,r=0.351).HLA-DR was positively correlated with CD163 protein expression(P=0.003,r=0.298).3、In invasive adenocarcinoma,CD68 protein expression was negatively correlated with vascular invasion and lymph node metastasis(r=-0.208,P=0.042).HLA-DR protein expression was negatively correlated with tumor pathological grade(r=-0.210,P=0.040)and lymph node metastasis(r=-0.228,P=0.025).CD163 protein expression was positively correlated with tumor T stage(r=0.437,P=0.013).There was no correlation among the others(P>0.05).Conclusion:1、During the development and progression of lung adenocarcinoma,the expression levels of CD163 and e NOS proteins both increased gradually.It is speculated that the infiltration density of M2-type TAMs with CD163 as the marker increased gradually during the progression of lung adenocarcinoma,and the development of lung adenocarcinoma may be related to the interaction of these two proteins.2、The interstromal expressions of CD68 and HLA-DR in invasive adenocarcinoma were significantly lower than those in preinvasive lesions.It was speculated that the infiltration density of M1-type TAMs with HLA-DR as markers gradually decreased during the progression of lung adenocarcinoma,and the infiltration density of broad-spectrum macrophages with CD68 as markers also gradually decreased during the progression of lung adenocarcinoma.These two proteins may inhibit the progression of lung adenocarcinoma.3、In invasive adenocarcinoma,the expressions of CD68、HLA-DR and CD163 proteins were correlated with certain pathological parameters(tumor T stage,pathological grade,vascular invasion,lymph node metastasis).