烟草烟雾暴露对肺腺癌患者外周血HDAC2、IL-8和TNF-α表达的影响

Effects of Tobacco Smoke Exposure on HDAC2,IL-8 and TNF-α Expression in Peripheral Blood of Patients with Lung Adenocarcinoma

目的探讨烟草烟雾暴露对肺腺癌患者外周血组蛋白去乙酰化酶2(HDAC2)、白细胞介素8(IL-8)、肿瘤坏死因子α(TNF-α)表达的影响及其相互关系。方法收集广西医科大学第一附属医院和附属肿瘤医院2014年4月至2015年3月术后病理确诊为肺腺癌的病例73例,术前均行肺功能检查;收集同期无烟草烟雾暴露无慢性阻塞性肺疾病(简称慢阻肺)的健康志愿者14例。根据有无烟草烟雾暴露及肺功能分为正常对照组(A组,14例)、无烟草烟雾暴露无慢阻肺肺腺癌组(B组,19例)、烟草烟雾暴露无慢阻肺肺腺癌组(C组,33例)、烟草烟雾暴露合并慢阻肺肺腺癌组(D组,21例)。实时荧光PCR检测各组外周血单核细胞(PBMCs)中HDAC2 mRNA、IL-8 mRNA、TNF-αmRNA的表达,ELISA检测各组外周静脉血清中IL-8、TNF-α的含量。结果与A组比较,B组PBMCs中HDAC2 mRNA的表达差异无统计学意义(P>0.05),C组、D组PBMCs中HDAC2mRNA的表达均下调(P<0.05),其中D组下调最明显。与A组比较,各肺腺癌组PBMCs中IL-8mRNA、TNF-αmRNA的表达以及外周静脉血清中IL-8、TNF-α的浓度均显著上调(P<0.05),且D组上调最明显。肺腺癌患者PBMCs中HDAC2 mRNA的表达在性别、年龄、TNM分期方面的差异均无统计学意义(P>0.05);PBMCs中IL-8 mRNA、TNF-αmRNA的表达以及血清IL-8、TNF-α的含量在性别、年龄方面的差异无统计学意义(P>0.05),在Ⅲ期患者PBMCs中的表达及血清中含量均较Ⅰ、Ⅱ期高(P<0.05),Ⅰ期与Ⅱ期比较差异无统计学意义(P>0.05)。结论烟草烟雾暴露导致肺腺癌患者外周血HDAC2表达下调,IL-8、TNF-α表达上调,加重炎症反应,在合并慢阻肺者表现更明显,可能与肺腺癌的预后有关。

Objective To investigate the effects of tobacco smoke exposure on histone deacetylase 2（HDAC2）,interleukin-8（ IL-8） and tumor necrosis factor-α（ TNF-α） expression in peripheral blood of patients with lung adenocarcinoma and analyze the relationships among them. Methods Seventy-three cases diagnosed as lung adenocarcinoma were collected in the First Affiliated Hospital and Affiliated Tumor Hospital of Guangxi Medical University from April 2014 to March 2015. All patients underwent lung function test preoperatively. Fourteen healthy volunteers without tobacco smoke exposure and chronic obstructive pulmonary disease（ COPD） were recruited as healthy control. According to the lung function and tobacco smoke exposure,all cases were divided into four groups,ie. a healthy control group（ group A,14 cases）,a group without tobacco smoke exposure and COPD（ group B,19 cases）,a group with tobacco smoke exposure and without COPD（ group C,33 cases）,and a group with tobacco smoke exposure and COPD（ group D,21cases）. The expressions of HDAC2 mRNA,IL-8 mRNA and TNF-α mRNA in peripheral blood mononuclear cells（ PBMCs） were detected by real-time polymerase chain reaction（ PCR）. The contents of IL-8 and TNF-α in serum were detected by ELISA. Results Compared with group A,the HDAC2 mRNA expression in PBMCs had no difference in group B（ P 〉 0. 05）,and was down-regulated significantly in group C and D（P 〈0. 05）,which in group D was the most obvious. Compared with group A,the expressions of IL-8 mRNA and TNF-α mRNA in PBMCs and the contents of IL-8 and TNF-α in serum were significantly higher in all lung adenocarcinoma patients（ all P 〈 0. 05）,and the up-regulation was more obvious in group D. The relative expression of HDAC2 mRNA in PBMCs showed no significant difference with respect to age,gender or TNM stage（ P 〉 0. 05）. IL-8 and TNF-α in PBMCs and serum showed no significant difference with respect to age and gender（ P 〉 0. 05）,and were higher in the patients with TNM stage Ⅲ lung adenocarcinoma than those with stageⅠand Ⅱ（ P 〈 0. 05）,with no obvious difference between stage Ⅰ and stage Ⅱ（ P 〉 0. 05）.Conclusion Tobacco smoke exposure causes lower expression of HDAC2 and over-expression of IL-8 and TNF-α in peripheral blood of patients with lung adenocarcinoma,can aggravate inflammatory response especially when complicated with COPD,which may be related to the prognosis of lung adenocarcinoma.