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目的:探讨不同分期非小细胞肺癌(non-small cell lung cancer,NSCLC)肿瘤微环境中IFN-γ、TGF-β1和吲哚胺-2,3-双加氧酶(indoleamine-2,3-dioxygenase,IDO)表达的变化及IFN-γ、TGF-β1表达与IDO表达的相关性。方法:选取2013年1月至2015年6月间昆明医科大学第一附属医院胸外科手术切除或纤维支气管镜取得的107例NSCLC患者肿瘤组织(实验组)和19例肺部外伤患者的正常肺组织(对照组)进入研究,实验组按2010年AJCC第七版肺癌分期标准分为4组:1组,Ⅰ期患者28例;2组,Ⅱ期患者26例;3组,Ⅲ期患者28例;4组,Ⅳ期患者25例。ELISA法检测组织中IFN-γ、TGF-β1、IDO蛋白浓度;免疫组化染色检测组织中IDO表达水平;分析IFN-γ、TGF-β1浓度与IDO浓度的相关性,分析肺癌组织中IDO、IFN-γ和TGF-β1表达间的相关性。结果:与对照组相比,Ⅰ期NSCLC组织中IFN-γ的浓度显著升高(P<0.05),而Ⅲ、Ⅳ期组织中IFN-γ浓度显著降低(P<0.05),并且Ⅳ期浓度显著低于Ⅲ期(P<0.05);IDO浓度变化与TGF-β1相似,在Ⅰ期NSCLC肿瘤组织中的浓度与正常肺组织无显著差异(P>0.05),但在Ⅱ、Ⅲ、Ⅳ期肿瘤组织中浓度显著高于正常肺组织(P<0.05),且随分期升高而升高。Pearson相关分析显示,正常组织、Ⅰ期NSCLC肿瘤组织中IDO的浓度与IFN-γ浓度呈正相关(r=0.969,P<0.01;r=0.853,P<0.01),与TGF-β1无相关性。但Ⅱ、Ⅲ、Ⅳ期肿瘤组织中IDO的浓度与TGF-β1浓度呈正相关(r=0.678,P<0.01;r=0.810,P<0.01;r=0.630,P=0.01),与IFN-γ无相关性。结论:早期NSCLC患者免疫微环境中IFN-γ增高,但随着疾病进展,患者免疫力降低,IFN-γ表达减少,IDO、TGF-β1表达增加,早期IDO表达可能与IFN-γ有关,而晚期则可能与TGF-β1有关。
Objective: To investigate the role of IFN-γ, TGF-β1 and indole-2,3-dioxygenase (indoleamine-2,3-) in different stages of non-small cell lung cancer (NSCLC) tumor microenvironment. Expression of dioxygenase, IDO) and the correlation between IFN-γ, TGF-β1 expression and IDO expression. METHODS: From January 2013 to June 2015, the thoracic surgical resection of the First Affiliated Hospital of Kunming Medical University or the bronchoscope obtained 107 cases of NSCLC tumor tissues (experimental group) and 19 cases of normal lungs of patients with lung injury. The study group (control group) entered the study. The experimental group was divided into four groups according to the 2010 AJCC seventh edition lung cancer staging criteria: group 1, group I patients in 28 cases; group 2, stage II patients in 26 cases; group 3, stage III patients 28 Cases; 4 groups, 25 patients with stage IV. ELISA was used to detect the concentration of IFN-γ, TGF-β1 and IDO in the tissue. The expression of IDO was detected by immunohistochemical staining. The correlation between IFN-γ, TGF-β1 and IDO concentration was analyzed. The IDO in lung cancer was analyzed. Correlation between IFN-γ and TGF-β1 expression. Results: Compared with the control group, the concentration of IFN-γ in the stage I NSCLC tissue was significantly increased (P<0.05), while the concentration of IFN-γ in the stage III and IV tissues was significantly decreased (P<0.05), and the IV stage concentration. Significantly lower than phase III (P<0.05); IDO concentrations were similar to those of TGF-β1, and there was no significant difference in the concentration of IDO NSCLC tumor tissues with normal lung tissue (P>0.05), but in phase II, III, IV The concentration in tumor tissue was significantly higher than that in normal lung tissue (P<0.05), and it increased with the increase of stage. Pearson correlation analysis showed that there was a positive correlation between the concentration of IDO and the concentration of IFN-γ in normal tissues and stage I NSCLC tumors (r=0.969, P<0.01; r=0.853, P<0.01), and there was no correlation with TGF-β1. However, the IDO concentrations in stage II, III, and IV tumors were positively correlated with TGF-β1 levels (r=0.678, P<0.01; r=0.810, P<0.01; r=0.630, P=0.01), and IFN-γ. No correlation. Conclusion: IFN-γ in the immune microenvironment of patients with early NSCLC increased, but as the disease progresses, the patient’s immunity is reduced, the expression of IFN-γ is decreased, and the expression of IDO and TGF-β1 is increased. The early expression of IDO may be related to IFN-γ. The late stage may be related to TGF-β1.