外泌体hsa_circRNA_042882在急性呼吸窘迫综合征中的诊断价值及与预后的关系

Diagnostic value of exosome hsa_circRNA_042882 in acute respiratory distress syndrome:Relationship with disease severity and prognosis

目的探讨外泌体hsa_circRNA_042882在急性呼吸窘迫综合征(ARDS)中的诊断价值及与预后的关系。方法回顾性选取2020年1月至2021年12月南京中医药大学附属医院重症监护室收治的ARDS患者113例,设为ARDS组。另选同院体检健康者53名作为正常组。按照氧合指数的水平不同分为轻度组(氧合指数200~300 mmHg,n=37)、中度组(氧合指数>100~200 mmHg,n=51)和重度组(氧合指数≤100 mmHg,n=25)。按照入院28 d内是否死亡将患者分为生存组(n=92)和死亡组(n=21)。收集患者的临床资料,观察血清外泌体的形态,qRT-PCR检测血清外泌体中circRNA_042882的表达,对不同程度、不同预后的ARDS患者临床资料及血清外泌体circRNA_042882表达水平进行对比,采用Logistic回归分析分析ARDS预后的影响因素,Person相关分析circRNA_042882表达水平与氧合指数及急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)评分的相关性,采用受试者工作特征(ROC)曲线分析circRNA_042882表达水平、氧合指数APACHEⅡ评分对ARDS患者预后的诊断价值。结果透射电镜下观察ARDS组和正常组血清中外泌体呈茶盘状结构。ARDS组患者血清外泌体circRNA_042882表达水平为0.27±0.04,明显低于正常组(1.59±0.17),差异有统计学意义(P<0.05)。重度组、中度组的ARDS患者氧合指数和circRNA_042882水平显著低于轻度组,APACHEⅡ评分明显高于轻度组,差异均有统计学意义(P<0.05)。死亡组ARDS患者氧合指数和circRNA_042882表达水平分别为(151.98±22.89)mmHg、0.15±0.02,均显著低于生存组[(229.26±32.64)mmHg、0.73±0.07],APACHEⅡ评分为(24.18±6.95)分,明显高于生存组[(14.69±4.98)分],差异均有统计学意义(P<0.05)。氧合指数升高和circRNA_042882升高为ARDS患者预后的保护因素(P<0.05),APACHEⅡ评分为ARDS患者预后独立危险因素(P<0.05)。血清外泌体circRNA_042882表达水平与氧合指数呈正相关(r=0.295,P<0.001),血清外泌体circRNA_042882表达水平与APACHEⅡ评分呈负相关(r=-0.519,P<0.001);血清外泌体circRNA_042882表达水平、氧合指数及APACHEⅡ评分及三者联合预测ARDS预后的曲线下面积分别为0.892、0.838、0.797及0.859,以血清外泌体circRNA_042882表达水平预测价值为最高(P<0.001)。结论ARDS患者血清外泌体中circRNA_042882表达水平表达降低,与ARDS患者病情进展和预后相关,对ARDS患者预后具有一定的诊断价值。

Objective To investigate the diagnostic value of exosome hsa_circRNA_042882 in acute respiratory distress syndrome(ARDS)and the relationship between disease severity and prognosis.Methods A total of 113 ARDS patients admitted to the Intensive Care Unit of The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2020 to December 2021 were prospectively selected and they were divided into ARDS group.Fifty-three healthy subjects in the same hospital were selected as the normal group.According to the level of oxygenation index,it is divided into mild group(oxygenation index 200-300 mmHg,n=37),moderate group(oxygenation index>100-200 mmHg,n=51),and severe group(oxygenation index≤100 mmHg,n=25).Patients were divided into survival group(n=92)and death group(n=21)groups according to whether they died within 28 days of admission.The clinical data of patients were collected,and the expression of circRNA_042882 in serum exosomes was detected by qRT-PCR.The clinical data and serum exosomal circRNA_042882 levels of ARDS patients with different degrees and prognosis were compared,and the influencing factors of ARDS prognosis were analyzed by Logistic regression.The correlation between circRNA_042882 level and oxygenation index and acute physiology and chronic health status evaluationⅡ(APACHEⅡ)score was analyzed by Person correlation analysis.The diagnostic value of circRNA_042882 level and APACHEⅡscore in ARDS patients was analyzed by receiver operating characteristic(ROC)curve.Results Under transmission electron microscopy,the serum exosomes of ARDS group and normal group were observed to be tea tray structure.The expression level of serum exosome circRNA_042882 in ARDS group was 0.27±0.04,which was significantly lower than that in normal group(1.59±0.17),the difference was statistically significant(P<0.05).The oxygenation index and circRNA_042882 levels of ARDS patients in the severe and moderate groups were significantly lower than those in the mild group,and the APACHE II score was significantly higher than that in the mild group,and the differences were statistically significant(P<0.05).The oxygenation index and circRNA_042882 levels of ARDS patients in the death group were(151.98±22.89)mmHg and 0.15±0.02,respectively,which were significantly lower than those in the survival group[(229.26±32.64)mmHg and 0.73±0.07],the APACHE II score in the death group was(24.18±6.95)points,which was significantly higher than those in the survival group[(14.69±4.98)points],and the differences were statistically significant(P<0.05).The increase of oxygenation index and circRNA_042882 were protective factors for prognosis of ARDS patients(P<0.05),and APACHEⅡscore was independent risk factor for prognosis of ARDS patients(P<0.05).The expression level of serum exosome circRNA_042882 was positively correlated with oxygenation index(r=0.295,P<0.001),and the expression level of serum exosome circRNA_042882 was negatively correlated with APACHEⅡscore(r=-0.519,P<0.001).The expression level of serum exosome circRNA_042882,oxygenation index and APACHEⅡscore and their combined prediction of ARDS prognosis were 0.892,0.838,0.797 and 0.859,respectively.The expression level of serum exosome circRNA_042882 had the highest predictive value(P<0.001).Conclusion The decreased expression of circRNA_042882 in serum exosomes of ARDS patients is related to the progression and prognosis of ARDS patients,and has a certain diagnostic value for the prognosis of ARDS patients.