血浆ctDNA中HOXA7、SOX17甲基化联合影像学指标在肺癌早诊中的应用研究  

Application of radiological indicators combined with the methylation of HOXA7 and SOX17 in plasma circulating tumor DNA in the early diagnosis of lung cancer

作　　者：杨蕊菲 刘葆婧 武曼 冯飞雪 张雨馨 王战争 马艳侠 Yang Ruifei;Liu Baojing;Wu Man;Feng Feixue;Zhang Yuxin;Wang Zhanzheng;Ma Yanxia(School of Medical Technology,Shaanxi University of Chinese Medicine;Department of Laboratory Medicine,The Affiliated Hospital of Shaanxi University of Chinese Medicine)

机构地区：[1]陕西中医药大学医学技术学院,咸阳712046 [2]陕西中医药大学附属医院检验科,咸阳712000

出　　处：《重庆医科大学学报》2025年第3期403-408,共6页Journal of Chongqing Medical University

基　　金：陕西中医药大学省级大学生创新训练资助项目(编号:S202310716120)。

摘　　要：目的:探讨肺结节直径、影像学指标、癌胚抗原(carcinoembryonic antigen,CEA)、细胞角蛋白19片段(cytokeratin 19 fragment antigen,CYFRA21-1)、鳞状细胞癌抗原(squamous cell carcinoma antigen,SCC)等血清肿瘤标志物及循环肿瘤DNA(circulating tumor DNA,ctDNA)中HOXA7、SOX17甲基化联合诊断早期肺癌的价值。方法:选取2021年9月至2022年12月本院收治的恶性肺结节患者60例,良性肺结节患者60例,作为肺癌组和良性结节组,另择同期于我院行体格检查的80例健康体检者作为对照组。比较3组间患者结节直径、毛刺征、血清肿瘤标志物水平及血浆ctDNA HOXA7、SOX17甲基化率,并通过多因素回归分析筛选癌变患者的独立危险因素,得出预测模型方程,采用受试者工作特征(receiver operating characteristic,ROC)曲线评价模型的诊断效能。结果:肺癌组肺结节直径、毛刺征、CEA、ProGRP、CYFRA21-1、血清HOXA7及SOX17甲基化率明显高于良性结节组和对照组,肺癌组SCC明显高于对照组,差异有统计学意义(P均<0.05)。肺结节直径、毛刺征及血清ctDNA HOXA7、SOX17甲基化率是恶性肺结节的独立危险因素(P<0.05),建立预测模型为Y=e^(x)(/1+e^(x)),x=-7.233+(0.108×结节直径)+(3.860×毛刺征)+(0.021×HOXA7甲基化率)+(0.043×SOX17甲基化率)。预测模型的AUC为0.981,相较于单个指标显著提升,较Mayo模型、LCBP模型的AUC高,差异均有统计学意义(P<0.05)。结论:肺结节直径、毛刺征、ctDNA HOXA7、SOX17甲基化率检测对肺癌患者早诊具有较高的诊断价值,基于以上指标建立的预测模型可明显提升诊断效能。Objective:To investigate the value of diameter of pulmonary nodules,radiological indicators,serum tumor markers(CEA,CYFRA21-1,and SCC),and methylation of HOXA7 and SOX17 in circulating tumor DNA(ctDNA)in the early diagnosis of lung cancer.Methods:A total of 60 patients with malignant pulmonary nodules and 60 patients with benign pulmonary nodules who were admitted to our hospital from September 2021 to December 2022 were enrolled as lung cancer group and benign nodule group,respectively,and 80 healthy individuals who underwent physical examination in our hospital during the same period of time were enrolled as control group.The three groups were compared in terms of the diameter of nodules,spiculation sign,levels of serum tumor markers,and methylation rates of HOXA7 and SOX17 in plasma ctDNA,and a multivariate regression analysis was performed to identify the independent risk factors for carcinogenesis and establish a predictive model.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic performance of the model.Results:Compared with the benign nodule group and the control group,the lung cancer group had significantly higher diameter of pulmonary nodules,proportion of patients with spiculation sign,CEA,ProGRP,CYFRA21-1,and methylation rates of serum HOXA7,and SOX17,and the lung cancer group had a significantly higher level of SCC than the control group(all P<0.05).The diameter of pulmonary nodules,spiculation sign,and methylation rates of HOXA7 and SOX17 in serum ctDNA were independent risk factors for malignant pulmonary nodules(P<0.05),and a predictive model was established as Y=e^(x)(/1+e^(x)),where x=-7.233+(0.108×nodule diameter)+(3.860×spiculation sign)+(0.021×HOXA7 methylation rate)+(0.043×SOX17 methylation rate).The predictive model had an area under the ROC curve(AUC)of 0.981,with a significantly larger AUC than each indicator alone and the Mayo and LCBP models(P<0.05).Conclusion:The diameter of pulmonary nodules,spiculation sign,and methylation rates of HOXA7 and SOX17

关 键 词：肺癌 肿瘤标志物 循环肿瘤DNA 甲基化 

分 类 号：R734.2[医药卫生—肿瘤]