血清microRNA-198、microRNA-182联合呼出气VOCs在肺部占位性病变性质鉴别中的应用

Application of serum miRNA-198 and miRNA-182 combined with exhaled VOCs in differentiating space-occupying lesions of the lung

摘要:

目的 探讨血清microRNA-198（miRNA-198）、microRNA-182（miRNA-182）联合呼出气挥发性有机化合物（VOCs）在肺部占位性病变性质鉴别中的价值。方法 选取2019年3月—2022年1月贵州遵义医科大学第二附属医院胸外科收治的150例肺部占位性病变患者，依据病理诊断将其分为恶性组（85例）和良性组（65例）。比较两组患者一般资料；比较两组、不同临床分期肺癌患者血清miRNA-198、miRNA-182相对表达量；绘制受试者工作特征（ROC）曲线，分析血清miRNA-198、miRNA-182表达以预测肺癌发生的价值；比较两组患者呼出气VOCs检出情况；经一致性分析呼出气VOCs诊断肺癌的效能和血清miRNA-198、miRNA-182联合呼出气VOCs诊断肺癌的效能。结果 两组患者年龄、性别构成、BMI、吸烟史、饮酒史、病程、肿瘤家族史、基础疾病史、病变直径比较，差异均无统计学意义（P >0.05）。恶性组miRNA-198表达量低于良性组（P <0.05），miRNA-182表达量高于良性组（P <0.05）。ROC曲线分析结果，血清miRNA-198、miRNA-182表达量预测肺癌发生的敏感性分别为92.3%（95% CI：0.854，0.973）、95.3%（95% CI：0.820，0.988）；特异性分别为81.2%（95% CI：0.720，0.894）、95.4%（95% CI：0.910，0.976）。TNM Ⅰ、Ⅱ期患者miRNA-198相对表达量高于Ⅲ期、Ⅳ期患者（P <0.05），miRNA-182表达量低于Ⅲ期、Ⅳ期患者（P <0.05）；Ⅲ期患者miRNA-198相对表达量高于Ⅳ期患者（P <0.05），miRNA-182表达量低于Ⅳ期患者（P <0.05）。恶性组患者3-甲基戊烷、乙苯检出率高于良性组（P <0.05），环戊烷检出率低于良性组（P <0.05）。两组患者呼出气乙烯、丙酮、异戊二烯、甲基环戊烷、十三烷、甲苯、6-甲基-5-庚烯-2-酮、N，N-二甲基酰胺、壬烷、邻二甲苯、1，2，4-三甲苯、β-蒎烯、葵烷、萘、丁二酸甲酯、壬醛检出率比较，差异均无统计学意义（P >0.05）。以病理诊断为金标准，呼出气VOCs诊断肺癌的敏感性为78.8%（95% CI：0.703，0.814）、特异性为76.9%（95% CI：0.725，0.844）、准确率为78.0%（95% CI：0.745，0.827）。病理诊断为金标准，血清miRNA-198、miRNA-182联合呼出气VOCs诊断肺癌的敏感性为96.5%（95% CI：0.873，0.981）、特异性为84.6%（95% CI：0.795，0.867）、准确率为91.3%（95% CI：0.826，0.982）。结论 血清miRNA-198、miRNA-182联合呼出气VOCs在肺部占位性病变性质鉴别中具有一定价值，且联合检测诊断肺癌的敏感性、准确率更高。

Abstract:

Objective To explore the value of serum microRNA-198 (miRNA-198) and microRNA-182 (miRNA-182) combined with exhaled volatile organic compounds (VOCs) in differentiating space-occupying lesions of the lung.Methods The 150 patients with space-occupying lesions of the lung admitted to the Department of Thoracic Surgery of our hospital from March 2019 to January 2022 were selected and divided into malignant group (n = 85) and benign group (n = 65) according to pathological diagnosis. The general clinical data were compared between the two groups, and serum expressions of miRNA-198 and miRNA-182 were compared between the two groups and among patients with different stages of lung cancer. The values of serum expressions of miRNA-198 and miRNA-182 in predicting the occurrence of lung cancer were analyzed via the receiver operating characteristic (ROC) curves. The detection rates of specific exhaled VOCs were compared between the two groups. The consistency analysis was conducted to compare the efficacy of exhaled VOCs alone and that of serum miRNA-198 and miRNA-182 combined with exhaled VOCs in diagnosing lung cancer.Results There was no statistically significant difference in age, sex composition, body mass index (BMI), history of smoking, history of alcohol consumption, course of disease, family history of tumors, or average diameter of lesions between the two groups of patients (P > 0.05). Compared with the benign group, the serum level of miRNA-198 was lower (P < 0.05) and the serum level of miRNA-182 was higher in the malignant group (P < 0.05). As demonstrated by the ROC curve analysis, the sensitivities of serum expressions of miRNA-198 and miRNA-182 in predicting the occurrence of lung cancer were 0.923 (95% CI: 0.854, 0.973) and 0.953 (95% CI: 0.820, 0.988), with the specificities being 0.812 (95% CI: 0.720, 0.894) and 0.954 (95% CI: 0.910, 0.976). Compared with patients with TNM stage I and Ⅱ lung cancer, the serum expression of miRNA-198 was higher (P < 0.05) and the serum level of miRNA-182 was lower in patients with TNM stage Ⅲ and IV lung cancer (P < 0.05). Compared with patients with TNM stage IV lung cancer, the serum expression of miRNA-198 was higher (P < 0.05) and that of miRNA-182 was lower in patients with stage IV lung cancer (P < 0.05). The detection rates of exhaled cyclopentane, 3-methylpentane and ethylbenzene were different between the malignant group and the benign group (P < 0.05). Specifically, the detection rates of 3-methylpentane and ethylbenzene were higher and the detection rate of cyclopentane was lower in the malignant group than in the benign group (P < 0.05). There was no difference in the detection rates of ethylene, acetone, isoprene, methylcyclopentane, tridecane, toluene, 6-methyl-5-hepten-2-one, N,N-dimethylformamide, nonane, o-xylene, 1,2,4-trimethylbenzene, β-pinene, decane, naphthalene, methyl succinate, and nonanal between the two groups (P > 0.05). With pathological diagnosis set as the gold standard, the sensitivity, specificity, and accuracy of exhaled VOCs in the diagnosis of lung cancer were 0.788 (95% CI: 0.703, 0.814), 0.769 (95% CI: 0.725, 0.844), and 0.780 (95% CI: 0.745, 0.827), and those of serum miRNA-198 and miRNA-182 combined with exhaled VOCs in the diagnosis of lung cancer were 0.965 (95% CI: 0.873, 0.981), 0.846 (95% CI: 0.795, 0.867), and 0.913 (95% CI: 0.826, 0.982), respectively.Conclusions The combination of serum miRNA-198 and miRNA-182 and exhaled VOCs is of certain value in differentiating space-occupying lesions of the lung, and the combined detection exhibits higher sensitivity and accuracy in the diagnosis of lung cancer.