CA199、CEA及cfDNA的联合检测对胆管癌的辅助诊断价值Diagnostic value of combined detection of CA199,CEA and plasma cell-free DNA for cholangiocarcinoma
莫迪;李梦雨;李华洋;王志龙;李丽娟;金红;
摘要(Abstract):
目的通过检测胆管癌、良性胆管疾病患者和健康人血液中的肿瘤标志物糖类抗原199(CA199)、癌胚抗原(CEA)和循环游离DNA(cfDNA)的水平,探讨联合检测以上3项指标在胆管癌的诊断中的辅助价值。方法收集2018年1月至2019年8月间哈尔滨医科大学附属肿瘤医院和牡丹江医学院附属红旗医院就诊的45例胆管癌患者、40例良性胆管疾病患者和45例健康人的血清和血浆。用化学发光法检测三组人群的血清肿瘤标志物CA199、CEA的水平;用实时荧光定量PCR的方法定量检测三组人群血浆中的cfDNA的水平。分析以上3个指标在三组人群中的表达水平差异;采用ROC曲线分析法比较3种血液分子标志物单独及联合检测在胆管癌中的诊断价值。结果胆管癌患者血清CA199水平和血浆cfDNA水平明显高于良性胆管疾病组和健康人组(P<0.05),CEA水平与良性胆管疾病组和健康人组没有统计学差异(P>0.05);良性胆管疾病组CA199和CEA和cfDNA水平与健康人比较,差异均没有统计学意义。ROC曲线显示,联合检测CA199、CEA和cfDNA的诊断敏感性和曲线下面积(AUC)均明显高于单独检测这3种肿瘤标志物的结果,联合检测的特异性均高于CA199和CEA单独检测的特异性,但低于cfDNA单独检测的特异性。由于CA199和CEA两项指标的参考值已知,计算出的cfDNA临床截断点(cut-off值或临界值)为18.06 ng/mL。结论与单独检测相比较,联合检测血液中CA199、CEA和cfDNA对于诊断胆管癌有更高的辅助价值。
关键词(KeyWords): CA199;cfDNA;胆管癌;诊断;液体活检
基金项目(Foundation): 红旗科研基金(2018HQ-03);; 牡丹江医学院研究生创新科研项目基金(2018YJSCX-29MY)
作者(Authors): 莫迪;李梦雨;李华洋;王志龙;李丽娟;金红;
DOI: 10.13799/j.cnki.mdjyxyxb.2020.03.005
参考文献(References):
- [1] LOOSN S H,RODERBURG C,KAUERTZ K L,et al.CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma[J].Scientific Reports,2017,7(1):169-175.
- [2] LARUSSO N F,PISARELLOM J L,GRADILONE S A.Primary Cilia in Tumor Biology:The Primary Cilium as a Therapeutic Target in Cholangiocarcinoma[J].Current Drug Targets,2017,18(8):3212-3217.
- [3] HUANG Y F,CHEN Y J,FAN T C,et al.Analysis of microbial sequences in plasma cell-free DNA for early-onset breast cancer patients and healthy females[J].Bmc Medical Genomics,2018,11(1):33-41.
- [4] LI Y,LI D J,CHEN J,et al.Application of Joint Detection of AFP,CA19-9,CA125 and CEA in Identification and Diagnosis of Cholangiocarcinoma[J].Asian Pacific Journal of Cancer Prevention Apjcp,2015,16(8):3451-3455.
- [5] LEE S J,KIM J E,KIM S T,et al.The Correlation Between Serum Chemokines and Clinical Outcome in Patients with Advanced Biliary Tract Cancer[J].Translational Oncology,2018,11(2):353-357.
- [6] 马婉红.血清CA199和CEA联合检测对胆管癌的诊断价值分析[J].临床医药文献电子杂志,2016,3(3):577-578.
- [7] WEN K C,JIA J L,GONG H H,et al.Preoperative serum CA199 levels is an independent prognostic factor in patients with resected hilar cholangiocarcinoma[J].Int J Clin Exp Pathol,2013,7(11):7890-7898.
- [8] 李绵绵,蔡锚,余坚,等.应用微滴式数字PCR定量检测结直肠癌患者血浆循环游离DNA[J].中国卫生检验杂志,2018,28(13):1579-1582.
- [9] YAN W,ZHANG A,POWELLM J.Genetic alteration and mutation profiling of circulating cell-free tumor DNA (cfDNA) for diagnosis and targeted therapy of gastrointestinal stromal tumors[J].Chinese Journal of Cancer,2016,35(7):342-349.
- [10] ELSHAFEY S S,MAHMOUD A A.Serum circulating cell free DNA as potential diagnostic and prognostic biomarker in non small cell lung cancer[J].Biochemistry and Biophysics Reports,2018,15(6):45-51.
- [11] XIA S,HUANG C C,LE M,et al.Genomic variations in plasma cell free DNA differentiate early stage lung cancers from normal controls[J].Lung Cancer,2015,90(1):78-84.
- [12] BARTAK B K,KALMAR A,GALAMB O,et al.Blood Collection and Cell-Free DNA Isolation Methods Influence the Sensitivity of Liquid Biopsy Analysis for Colorectal Cancer Detection[J].Pathology oncology research,2019,25(3):915-923.
- [13] OPENSHAW M R,PAGE K,FERNANDEZ G D,et al.The role of ctDNA detection and the potential of the liquid biopsy for breast cancer monitoring[J].Expert Review of Molecular Diagnostics,2016,16(7):751-755.
- [14] 苏德望,付先东,于佳楠,等.血清糖类抗原19-9、癌胚抗原在胆管癌诊断中的应用价值[J].中国实验诊断学,2017,21(10):1693-1695.
- [15] 汪富涛.胆汁中肿瘤标记物(CA199、AFP、CEA)的检测对胆管癌诊断的临床意义[D].昆明:昆明医科大学,2013.