肺癌合并支气管哮喘患者白细胞介素-13和骨膜蛋白表达水平与气道重塑严重程度的相关性分析

Correlation analyses between expression levels of interleukin-13 and periosteal protein and severity of airway remodeling in patients with lung cancer and bronchial asthma

目的探讨肺癌合并支气管哮喘患者白细胞介素-13(IL-13)和骨膜蛋白表达水平与气道重塑严重程度的相关性.方法回顾性分析2018年1月至2020年1月在中南大学湘雅医学院附属海口医院就诊的94例行肺叶切除术肺癌患者的临床资料.结合《支气管哮喘防治指南(基层版)》相关诊断标准筛选出合并支气管哮喘的肺癌患者40例作为合并支气管哮喘组,无合并症的54例肺癌患者作为无合并症组.收集所有患者的一般资料,并检测肺功能指标〔1秒用力呼气容积占预计值百分比(FEV1%pred)、1秒用力呼气容积/用力肺活量比值(FEV1/FVC)〕.手术后取远离癌巢的气道组织进行染色观察,检测杯状细胞计数、成纤维细胞计数、基底膜厚度、胶原蛋白沉积量等气道重塑指标,采用免疫组化法检测IL-13和骨膜蛋白表达水平.采用Spearman等级相关性分析方法对IL-13、骨膜蛋白表达量与气道重塑指标和肺功能指标进行相关性分析.结果合并支气管哮喘组杯状细胞计数(个:27.94±7.82比11.08±3.05)、成纤维细胞计数(个:16.77±2.37比6.23±1.39)、基底膜厚度(μm:10.53±1.59比4.37±1.14)、胶原蛋白沉积量(μm:8.81±1.92比3.20±1.07)均显著高于无合并症组(均P<0.05);合并支气管哮喘组FEV1%pred〔(59.12±10.82)%比(102.38±11.22)%〕、FEV1/FVC〔(64.90±7.78)%比(87.40±4.83)%〕均显著低于无合并症组(均P<0.05);IL-13和骨膜蛋白与杯状细胞计数、胶原蛋白沉积量、基底膜厚度、成纤维细胞计数均呈正相关(IL-13:r值分别为0.752、0.641、0.769、0.762,P值分别为0.000、0.001、0.000、0.000;骨膜蛋白:r值分别为0.671、0.549、0.620、0.520,P值分别为0.000、0.006、0.001、0.008),与FEV1%pred、FEV1/FVC呈负相关(IL-13:r值分别为-0.765、-0.743,P值分别为0.000、0.000;骨膜蛋白:r值分别为-0.601、-0.650,P值分别为0.002、0.001).结论肺癌合并支气管哮喘患者气道中IL-13和骨膜蛋白表达水平显著上调与患者气道重塑有关,二者联合检测可作为评估支气管哮喘患者病情严重程度和预后的生物标志物.

Objective To investigate the correlations between the expression levels of interleukin-13(IL-13)and periosteal protein and the severity of airway remodeling in lung cancer patients with bronchial asthma.Methods The clinical data of 94 lung cancer patients who underwent lung lobectomy in Affiliated Haikou Hospital of Xiangya Medical College,Central South University from January 2018 to January 2020 were retrospectively analyzed.According to the related diagnostic criteria in Guidelines for Prevention and Treatment of Bronchial Asthma,the 40 lung cancer patients with bronchial asthma were screened out and assigned in the bronchial asthma group,while the 54 lung cancer patients without the comorbidity were in the non-comorbidity group.The general informatory data of all patients were collected and the lung function indexes[percentage to predicted value of forced end expiratory volume in 1 second(FEVl%pred),forced end expiratory volume in 1 second/fbrced vital capacity ratio(FEV1/FVC)]were detected.After operation,the airway tissue at remote area from the cancer nest of patients was taken and stained to be observed,and the airway remodeling indicators such as goblet cell count,fibroblast count,basement membrane thickness and amount of collagen deposition were investigated.The expression levels of IL-13 and periosteal protein were detected by immunohistochemical method,and the correlations between the expression levels of airway remodeling and lung function indicators were analyzed by Spearman grade correlation analyses.Results The goblet cell count(cells:27.94±7.82 vs.11.08±3.05),fibroblast count(cells:16.77±2.37 vs.6.23±1.39),basement membrane thickness(p.m:10.53±1.59 vs.4.37±1.14),and collagen deposition amount(pim:8.81±1.92 vs.3.20±1.07)in the bronchial asthma group were significantly higher than those in the non-comorbidity group(all P<0.05);FEVl%pred[(59.12±10.82)%vs.(102.38±11.22)%]and FEV1/FVC[(64.90±7.78)%vs.(87.40±4.83)%]in the bronchial asthma group were significantly lower than those in the non-comorbidity group(both P<0.05);the expression levels of IL-13 and periosteal protein were positively correlated with goblet cell count,collagen protein deposition amount,basement membrane thickness and fibroblast count(IL-13:r values were 0.752,0.641,0.769,0.762,P values were 0.000,0.001,0.000,0.000;periosteal protein:r values were 0.671,0.549,0.620,0.520,P values were 0.000,0.006,0.001,0.008),and were negatively correlated with FEVl%pred and FEV1/FVC(IL-13:r values were-0.765,-0.743,P values were 0.000,0.000;periosteal protein:r values were-0.601,-0.650,P values were 0.002,0.001).Conclusions The significant up-regulation of IL-13 and periosteal protein expressions in the airway of lung cancer patients with bronchial asthma is related to ainvay remodeling.The detections of the two factors can be used as biomarkers to assess the severity and prognosis of lung cancer patients with bronchial asthma.