胸腔积液外泌体miR-506-3p联合腺苷脱氨酶检测在结核性胸膜炎的早期诊断及预后评估中的价值

doi:10.19871/j.cnki.xfcrbzz.2024.02.004

摘要/Abstract

摘要： 目的分析胸腔积液外泌体miR-506-3p联合腺苷脱氨酶（adenosine deaminase,ADA）在结核性胸膜炎的早期诊断及预后评估中的价值。方法选取2021年8月至2023年3月就诊于沧州市人民医院的90例结核性胸膜炎患者作为结核组,另选同期于沧州市人民医院就诊的50例非结核性胸膜炎（肺炎旁胸腔积液、恶性胸腔积液等）患者作为非结核组,对比两组临床资料与胸腔积液外泌体miR-506-3p、ADA水平,经多因素Logistic回归分析影响结核性胸膜炎发生的危险因素。根据治疗3个月后患者预后情况,将结核组分为预后良好组（72例）、预后不良组（18例）,对比两组胸腔积液外泌体miR-506-3p、ADA水平。经Pearson相关性分析,并绘制受试者操作特征曲线（receiver operating characteristic curve,ROC曲线）,分析胸腔积液外泌体miR-506-3p、ADA水平及二者联合预测结核性胸膜炎发生及患者预后的价值。结果结核组患者胸腔积液ADA水平比非结核组高,胸腔积液外泌体miR-506-3p水平比非结核组低（P<0.05）;经多因素Logistic回归分析发现,胸腔积液ADA水平高[OR=1.205（95%CI 1.105~1.313）]是结核性胸膜炎发生的危险因素（P<0.05）,外泌体miR-506-3p水平高表达[OR=0.320（95%CI 0.158~0.658）]是结核性胸膜炎发生的保护因素（P<0.05）;预后不良组患者胸腔积液ADA水平比预后良好组高,胸腔积液外泌体miR-506-3p水平比预后良好组低（P<0.05）;绘制ROC曲线发现,胸腔积液ADA、外泌体miR-506-3p水平及二者联合预测结核性胸膜炎发生的曲线下面积（area under curve,AUC）为0.729（95%CI 0.640~0.818）、0.810（95%CI 0.738~0.883）、0.874（95%CI 0.818~0.930）,预测结核性胸膜炎患者不良预后的AUC为0.892（95%CI 0.806~0.978）、0.924（95%CI 0.868~0.981）、0.942（95%CI 0.875~1.000）;Pearson相关性显示,胸腔积液ADA与外泌体miR-506-3p水平呈负相关（r=-0.335,P=0.001）。结论结核性胸膜炎患者胸腔积液外泌体miR-506-3p呈低表达、ADA呈高表达,二者之间为负相关,且miR-506-3p联合ADA可有效预测结核性胸膜炎患者不良预后的发生。

关键词: 结核性胸膜炎, 胸腔积液, 外泌体miR-506-3p, 腺苷脱氨酶, 诊断, 预后

Abstract: Objective To evaluate the value of pleural fluid exosome miR-506-3p combined with adenosine deaminase (ADA) in the early diagnosis and prognosis of tuberculous pleurisy. Method Ninety patients with tuberculous pleurisy admitted to Cangzhou People's Hospital from August 2021 to March 2023 were selected as the tuberculosis group, and 50 patients with non-tuberculous pleurisy (parapneumonic pleural effusion, malignant pleural effusion, etc.) admitted to our hospital during the same period were selected as the non-tuberculosis group. The clinical data and the levels of exosomes miR-506-3p and ADA in pleural fluid were compared between the two groups, and the risk factors affecting the occurrence of tuberculous pleurisy were analyzed by multivariate Logistic regression.According to the prognosis of patients after 3 months of treatment, the tuberculosis group was divided into a good prognosis group and a poor prognosis group. The levels of exosomes miR-506-3p and ADA in pleural fluid of the two groups were compared, and the correlation between the two groups was analyzed by Pearson, and the ROC curve was drawn. To analyze the value of pleural fluid exosome miR-506-3p and ADA levels and their combination in predicting the occurrence and prognosis of tuberculous pleurisy. Result ADA level in pleural fluid in TB group was higher than that in non-TB group, and exosome miR-506-3p in pleural fluid was lower than that in non-TB group (P<0.05). Multivariate Logistic regression analysis showed that ADA[OR=1.205 (95%CI 1.105-1.313)] was a risk factor for tuberculous pleurisy(P<0.05). The expression of exosome miR-506-3p [β=0.320 (95%CI 0.158-0.658)] was a protective factor in the occurrence of tuberculous pleurisy(P<0.05). ADA of pleural fluid in poor prognosis group was higher than that in good prognosis group, and exosome miR-506-3p of pleural fluid was lower than that in good prognosis group (P<0.05). Drawing ROC curve found that, The AUC of pleural fluid ADA, exosome miR-506-3p and their combination for predicting the occurrence of tuberculous pleurisy were 0.729 (95%CI 0.640-0.818), 0.810 (95%CI 0.7388-0.883), 0.874 (95%CI 0.818-0.930). The AUC of pleural fluid ADA, exosome miR-506-3p and their combination in predicting the poor prognosis of patients with tuberculous pleurisy were 0.892 (95%CI 0.806-0.978), 0.924 (95%CI 0.868-0.981), 0.942 (95%CI 0.875-1.000). Pearson correlation showed that ADA in pleura was negatively correlated with exosome miR-506-3p (r=-0.335, P=0.001). Conclusion In patients with tuberculous pleurisy, the expression of pleural exosomes miR-506-3p is low and ADA is high, and the two are negatively correlated, and the combination of miR-506-3p and ADA can effectively predict the occurrence of poor prognosis in patients with tuberculous pleurisy.

Key words: Tuberculous pleurisy, Hydrothorax, Exosome miR-506-3p, Adenosine deaminase, Diagnosis, Prognosis

中图分类号:

R521.7

张银文, 曹新超, 谢荣景. 胸腔积液外泌体miR-506-3p联合腺苷脱氨酶检测在结核性胸膜炎的早期诊断及预后评估中的价值[J]. 新发传染病电子杂志, 2024, 9(2): 18-23.

Zhang Yinwen, Cao Xinchao, Xie Rongjing. Value of pleural effusion exosomes miR-506-3p combined with adenosine deaminase test in the early diagnosis and prognostic evaluation of tuberculous pleuritis[J]. Electronic Journal of Emerging Infectious Diseases, 2024, 9(2): 18-23.

参考文献

[1] 卢春容,谭卫国,陆普选,等.2023年WHO全球结核病报告:全球与中国关键数据分析[J/CD].新发传染病电子杂志,2023,8(6):73-78.
[2] LO CASCIO CM, KAUL V, DHOORIA S, et al.Diagnosis of tuberculous pleural effusions: A review[J]. Respir Med, 2021, 188:106607.
[3] LUO Y, XUE Y, GUO X, ET AL.Diagnostic value of pleural fluid t-spot for tuberculous pleurisy: an updated meta-analysis[J]. Tuberculosis (Edinb), 2020, 122:101941.
[4] MARÍN FRANCO JL, GENOULA M, CORRAL D, et al. Host-Derived Lipids from Tuberculous Pleurisy Impair Macrophage Microbicidal-Associated Metabolic Activity[J].Cell Rep, 2020, 33(13):108547.
[5] NÚÑEZ-JURADO D, RODRÍGUEZ-MARTÍN I, GUERRERO JM, et al. LDH/ADA ratio in pleural fluid for the diagnosis of infectious pleurisy[J]. Clin Exp Med, 2023, 23(8):5201-5213.
[6] LIANG LM, XIONG L, CHENG PP, et al.Splicing factor SRSF6 mediates pleural fibrosis[J]. JCI Insight, 2021, 6(10):e146197.
[7] 中华人民共和国国家卫生和计划生育委员会.肺结核诊断标准(WS288-2017)[J/CD].新发传染病电子杂志, 2018, 3(1):59-61.
[8] ZHANG X, BAO L, YU G, et al.Exosomes miRNA-profiling of pleural effusion in lung adenocarcinoma and tuberculosis[J]. Front Surg, 2023, 9:1050242.
[9] WANG Y, XU YM, ZOU YQ, et al.Identification of differential expressed PE exosomes miRNA in lung adenocarcinoma, tuberculosis, and other benign lesions[J]. Medicine (Baltimore), 2017 , 96(44):e8361.
[10] SASTRE B, CANAS JA, RDRIGO-MUNOZ JM, et al.Novel modulators of asthma and allergy:Exosomes and microRNAs[J]. Front Immunol, 2017, 8:826-835.
[11] GUIO H, ALIAGA-TOBAR V, GALARZA M, et al.Comparative Profiling of Circulating Exosomes Small RNAs Derived From Peruvian Patients With Tuberculosis and Pulmonary Adenocarcinoma[J].Front Cell Infect Microbiol, 2022, 12:909837.
[12] ZHANG M, WANG JY, LI L, et al.MiR-506 alleviates myocardial ischemia-reperfusion injury via targeting PI3K/AKT[J].Eur Rev Med Pharmacol Sci, 2020, 24(24):12896-12903.
[13] CHEN L, WANG X, JI C, et al.MiR-506-3p suppresses papillary thyroid cancer cells tumorigenesis by targeting YAP1[J].Pathol Res Pract, 2020, 216(12):153231.
[14] SHANG A, GU C, WANG W, et al.Exosomes circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis[J].Mol Cancer, 2020, 19(1):117.
[15] XIANG H, LUO M, HOU P, et al.miR-124-3p combined with miR-506-3p delay hepatic carcinogenesis via modulating sirtuin 1[J].Biomarkers, 2021, 26(3):196-206.
[16] 陈思达, 卓宋明, 李娜, 等. 痰液miR-155检测作为诊断结核分枝杆菌感染标志物的研究[J].中国热带医学, 2020, 20(4):359-363.
[17] KIM SB, SHIN B, LEE JH, et al.Pleural fluid ADA activity in tuberculous pleurisy can be low in elderly, critically ill patients with multi-organ failure[J].BMC Pulm Med, 2020, 20(1):13.