STC1、TWEAK、miR-183在COPD患者中的表达及相关性研究

目的 探讨斯钙素1(stanniocalcin 1，STC1)、肿瘤坏死因子相关弱凋亡诱导因子(tumor necrosis factor-like weak inducer of apoptosis，TWEAK)、微小RNA(microRNA，miRNA)-183在慢性阻塞性肺疾病(chronic obstructive pulmonary disease，COPD)患者中的表达及相关性。 方法 选取COPD患者114例为COPD组，根据气流受限程度分为重度组(n=23)、中度组(n=48)、轻度组(n=43)，并根据预后情况分为病死组(n=22)和存活组(n=92)，另选取同期体检健康者63例为对照组。检查受试者肺功能［第1秒用力呼气容积(forced expiratory volume in one second，FEV1)、FEV1/用力肺活量(forced vital capacity，FVC)］，测定血清STC1、TWEAK、miR-183、丙二醛(malondialdehyde，MDA)、超氧化物歧化酶(superoxide dismutase，SOD)、白细胞介素(interleukin，IL)、IL-8水平。Pearson相关性分析COPD组血清STC1、TWEAK、miR-183水平与肺功能和血清MDA、SOD、IL-6、IL-8水平的相关性。ROC曲线分析血清STC1、TWEAK、miR-183水平对COPD患者预后不良的预测价值。 结果 与对照组比较，COPD组FEV1、FEV1/FVC和血清STC1、SOD水平明显降低，TWEAK、miR-183、MDA、IL-6、IL-8水平明显升高(P＜0.05)。轻、中、重度组血清STC1、SOD水平依次降低，TWEAK、miR-183、MDA、IL-6、IL-8水平依次升高(P＜0.05)。COPD组血清STC1水平与FEV1、FEV1/FVC、SOD呈正相关，与MDA、IL-6、IL-8呈负相关(P＜0.05)，TWEAK、miR-183水平与FEV1、FEV1/FVC、SOD呈负相关，与MDA、IL-6、IL-8呈正相关(P＜0.05)。STC1＋TWEAK＋miR-183(area under curve，AUC=0.919，95%CI：0.853~0.862)预测COPD患者预后不良的曲线下面积(area under curve，AUC)明显大于STC1(AUC=0.796，95%CI：0.710~0.866)、TWEAK(AUC=0.788，95%CI：0.702~0.859)、miR-183(AUC=0.798，95%CI：0.713~0.868)单独预测(P＜0.05)。 结论 COPD患者血清STC1水平降低，TWEAK、miR-183水平升高，可能通过氧化应激和炎症反应参与COPD病情进展，可作为患者预后不良预测指标。

The expression of STC1, TWEAK,and miR-183 in COPD patients and their correlation

Objective To investigate the expression of stanniocalcin 1(STC1), tumor necrosis factor-like weak inducer of apoptosis(TWEAK), and microRNA(miRNA)-183 in patients with chronic obstructive pulmonary disease(COPD) and their correlation.Methods In total, 114 COPD patients were selected as the COPD group, and divided into severe(n=23), moderate(n=48) and mild(n=43) groups according to the degree of airflow restriction, and divided into death(n=22) and survival(n=92) groups according to the prognosis. Another 63 healthy people undergoing physical examination during the same period were selected as the control group.The lung function ［forced expiratory volume in one second(FEV1), FEV1/forced vital capacity(FVC)］of the subjects was examined, and the levels of serum STC1, TWEAK, miR-183, malondialdehyde(MDA), superoxide dismutase(SOD), interleukin(IL) 6 and IL-8 were determined. Pearson correlation analysis was used to analyze the correlation between serum STC1, TWEAK, miR-183 levels and lung function and serum MDA, SOD, IL-6, and IL-8 levels in COPD group. The ROC curve was used to analyze the predictive value of serum STC1, TWEAK, and miR-183 levels in the poor prognosis of COPD patients.Results Compared with the control group, FEV1, FEV1/FVC and serum STC1, SOD levels in the COPD group were significantly reduced, while the levels of TWEAK, miR-183, MDA, IL-6, and IL-8 were significantly increased(P＜0.05).Serum STC1 and SOD levels in the mild, moderate and severe groups decreased sequentially, while the levels of TWEAK, miR-183, MDA, IL-6, and IL-8 increased sequentially(P＜0.05). Serum STC1 levels in the COPD group were positively correlated with FEV1, FEV1/FVC, and SOD, and negatively correlated with MDA, IL-6, and IL-8(P＜0.05). TWEAK and miR-183 levels were negatively correlated with FEV1, FEV1/FVC, and SOD, and positively correlated with MDA, IL-6, and IL-8(P＜0.05). The area under ROC curve (AUC) of STC1+TWEAK+miR-183(AUC=0.919, 95%CI: 0.853-0.862) in predicting poor prognosis of COPD patients was significantly greater than that of STC1(AUC=0.796, 95%CI: 0.710-0.866), TWEAK(AUC=0.788, 95%CI: 0.702-0.859), and miR-183(AUC=0.798, 95%CI: 0.713-0.868) alone(P＜0.05). Conclusion The serum STC1 level of patients with COPD decreases, and the levels of TWEAK and miR-183 increase. It may be involved in the progression of COPD through oxidative stress and inflammation, which can be used as predictors of poor prognosis for patients.