血浆循环游离DNA(cf_...细胞肺癌治疗疗效的临床价值_冯访梅.pdf

现代生物医学进展Progress in Modern Biomedicine Vol.23NO.1JAN.2023doi:10.13241/ki.pmb.2023.01.018血浆循环游离 DNA(cf DNA)联合癌胚抗原(CEA)在评估晚期非小细胞肺癌治疗疗效的临床价值*冯访梅1,2郭人花1刘中秋3陈琳4武宜婷2（1 南京医科大学第一附属医院 江苏 南京 210029；2 东南大学附属中大医院江北院区肿瘤科 江苏 南京 210000；3 东南大学附属中大医院江北院区药剂科 江苏 南京 210000；4 江苏省肿瘤医院 江苏 南京 210009）摘要 目的：研究血浆循环游离 DNA（cf DNA）联合癌胚抗原（CEA）在评估晚期非小细胞肺癌（NSCLC）治疗疗效中的临床价值。方法：选取我院 2019 年 1 月 2022 年 1 月收治的 96 例晚期 NSCLC 患者作为研究对象，所有患者均接受含铂双药化疗方案或放疗，评估治疗 6 个月后的临床疗效，根据疗效分为有效组与无效组，检测所有患者 cf DNA 及 CEA 水平并进行比较，单因素、多因素分析患者疗效的影响因素，并通过受试者工作特征曲线图（ROC）分析 cf DNA 及 CEA 对晚期 NSCLC 患者治疗疗效的评估价值。结果：本研究中 96 例患者均顺利完成化疗治疗，疗程结束后，有 54 例（56.25%）治疗有效，42 例（43.75%）治疗无效；无效组肿瘤 TNM 分期期、体力状况（PS）评分 24 分占比大于有效组（P0.05）；无效组患者 cf DNA 及 CEA 水平明显高于有效组（P0.05）；多因素 Logistic 回归分析显示，肿瘤分期期、PS 评分 24 分、cf DNA 及 CEA 高水平均为影响晚期 NSCLC 患者疗效的相关因素（P0.05）；ROC 曲线分析显示，cf DNA、CEA 对晚期 NSCLC 患者治疗后无效均有预测效能（P0.05），其中两指标联合预测的曲线下面积（AUC）最大，为 0.794，特异度、敏感度分别为 85.19%、78.57%。结论：治疗无效晚期非小细胞肺癌患者 cf DNA及 CEA 水平更高，肿瘤分期期、PS 评分 24 分、cf DNA 及 CEA 高水平均为晚期 NSCLC 患者疗效的影响因素，联合 cf DNA及 CEA 检测有利于对晚期 NSCLC 患者治疗疗效进行评估。关键词：血浆循环游离 DNA；癌胚抗原；晚期非小细胞肺癌；疗效评估中图分类号：R734.2文献标识码：A文章编号：1673-6273（2023）01-93-05Clinical Value of Circulating Cell-free DNA(cf DNA)Combined withCarcinoembryonic Antigen(CEA)on Rvaluating the Therapeutic Rfficacy ofAdvanced Non-small Cell Lung Cancer*FENG Fang-mei1,2,GUO Ren-hua1,LIU Zhong-qiu3,CHEN Lin4,WU Yi-ting2(1 the First Affiliated Hospital with Nanjing Medical University,Nanjing,Jiangsu,210029,China;2DepartmentofOncology,JiangbeiHospitalDistrict,ZhongdaHospitalAffiliatedtoSoutheastUniversity,Nanjing,Jiangsu,210000,China;3DepartmentofPharmacy,JiangbeiHospitalDistrict,ZhongdaHospitalAffiliatedtoSoutheastUniversity,Nanjing,Jiangsu,210000,China;4 Jiangsu Cancer Hospital,Nanjing,Jiangsu,210009,China)ABSTRACT Objective:To study the clinical value of combination of circulating cell-free DNA(cf DNA)and carcinoembryonicantigen(CEA)on evaluating the therapeutic efficacy of advanced non-small cell lung cancer(NSCLC).Methods:96 patients withadvanced NSCLC who were treated in the hospital between January 2019 and January 2022 were selected as the research subjects.Allpatients received platinum-containing dual-drug chemotherapy or radiotherapy,and the clinical efficacy after 6 months of treatment wasevaluated.According to the efficacy,the patients were classified onto effective group and ineffective group.The levels of cf DNA andCEA in all patients were detected and compared,and the influencing factors of efficacy were analyzed by univariate analysis and multi-variate analysis.Receiver operating characteristic curve(ROC)was used to analyze the evaluated value of cf DNA and CEA on the thera-peutic efficacy of patients with advanced NSCLC.Results:96 patients successfully completed chemotherapy treatment.After the end ofthe course of treatment,54 patients(56.25%)were treated effectively,and 42 patients(43.75%)were ineffective.The proportions oftumor TNM stage IV and physical status(PS)score of 2-4 points in ineffective group were higher than those in effective group(P0.05).The levels of cf DNA and CEA were also significantly higher than those in effective group(P0.05).Multivariate Logistic regressionanalysis showed that tumor stage IV,PS score of 2-4 points,and high levels of cf DNA and CEA were all related factors affecting theefficacy of patients with advanced NSCLC(P0.05).ROC curve analysis showed that cf DNA and CEA had predictive efficiencyon ineffectiveness in patients with advanced NSCLC after treatment(P0.05),and the area under the curve(AUC)of the combination of*基金项目：国家自然科学基金青年项目（8210012370）作者简介：冯访梅（1984-），女，本科，主治医师，E-mail:（收稿日期：2022-05-18 接受日期：2022-06-13）93现代生物医学进展Progress in Modern Biomedicine Vol.23NO.1JAN.2023the two indicators was the largest at 0.794,with the specificity of 85.19%and sensitivity of 78.57%.Conclusion:The levels of cf DNAand CEA in patients with advanced non-small cell lung cancer and ineffective treatment are higher,and tumor stage IV,PS score of 2-4points and high levels of cf DNA and CEA are the influencing factors for the efficacy of advanced NSCLC patients.The combination ofcf DNA and CEA is helpful for evaluating the therapeutic efficacy of patients with advanced NSCLC.Key words:Circulating cell-free DNA;Carcinoembryonic antigen;Advanced non-small cell lung cancer;Efficacy evaluationChinese Library Classification(CLC):R734.2Document code:AArticle ID:1673-6273（2023）01-93-05前言肺癌是常见的呼吸系统恶性肿瘤之一，具有发病率、死亡率高的特点，以老年人居多，其中非小细胞肺癌（NSCLC）占肺癌的 80%左右1,2。由于 NSCLC 早期无特异性表现，在诊疗过程中容易被忽视，并且 NSCLC 诊断缺乏特异性分子生物学指标，很大一部分患者在确诊时已处于中晚期，常存在远处转移，错过手术切除治疗的最佳时机3-5。NSCLC 治疗临床上以综合治疗结合个体化治疗为主，分子靶向治疗、免疫治疗、放疗等方式均在中晚期 NSCLC 中有应用，一定程度上能够使患者生存期延长，但由于对综合治疗后的疗效同样缺乏特异性评判指标，难以发现 NSCLC 复发转移，影响患者长期预后评估6。血浆循环游离 DNA（cf DNA）是一种由肿瘤细胞释放到血液循环系统中的无细胞状态的 DNA，可能来自于坏死、凋亡的肿瘤细胞，当机体感染炎症、肿瘤、自身免疫性疾病时，体内 cf DNA 水平会出现增加，多项研究显示，胃癌、卵巢癌等癌症患者体内 cfDNA 水平会异常升高7,8。癌胚抗原（CEA）为血清肿瘤标志物之一，其在肺癌患者血清中有所升高，检测 CEA 水平有助于对恶性肿瘤进行鉴别诊断、疗效评价等9。因此，本研究对 cf DNA联合 CEA 在评估晚期 NSCLC 治疗疗效的临床价值进行研究，现报告如下。1 资料与方法1.1 一般资料选取我院 2019 年 1 月 2022 年 1 月收治的 96 例晚期NSCLC 患者作为研究对象，其中男性