肝细胞癌患者经肝动脉化疗栓塞术后AFP、脱-γ-羧基凝血酶原水平的变化及其对治疗效果的预测价值
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摘要
目的探讨AFP联合脱-γ-羧基凝血酶原(DCP)在预测经肝动脉化疗栓塞术(TACE)疗效中的价值。方法回顾性分析2016年10月-2018年3月在苏州大学附属第一医院经接受TACE治疗的85例肝细胞癌(HCC)患者的临床资料。分析TACE术前、连续2次TACE术后患者血清AFP、DCP的水平变化,以mRECIST标准评价TACE治疗效果,将AFP、DCP水平变化情况与同期影像学(mRECIST标准)进行对照分析。计量资料经正态性检验,符合正态分布的2组间比较采用两独立样本t检验;不符合正态分布的数据2组间比较采用Mann-Whitney U检验。计数资料2组间比较采用χ2检验;等级计数资料2组间比较采用Mann-Whitney U检验。采用Spearman相关性分析探索mRECIST分级与AFP、DCP水平变化之间的相关性。采用受试者工作特征曲线分析各指标诊断缓解组的价值。结果依据mRECIST标准,缓解组38例,未缓解组31例。缓解组治疗后AFP和DCP均明显低于未缓解组(Z值分别为-3. 366、-4. 065,P值均<0. 05)。缓解组△AFP、△DCP、△AFP%及△DCP%与未缓解组比较,差异均有统计学意义(Z值分别为-4. 837、-5. 597、-4. 210、-5. 851,P值均<0. 001)。mRECIST分期与△AFP、△DCP均呈明显的负相关(rs分别为-0. 552、-0. 593,P值均<0. 001)。△AFP%用于诊断缓解组的受试者工作特征曲线下面积为0. 796,△DCP%为0. 912,△AFP%+△DCP%联合为0. 921,△AFP%+△DCP%的诊断价值最大。结论联合分析TACE前后血清AFP和DCP水平变化可评估肝细胞癌TACE的治疗效果。
Objective To investigate the value of alpha-fetoprotein( AFP) combined with des-γ-carboxy-prothrombin( DCP) in predicting the therapeutic effect of transarterial chemoembolization( TACE). Methods A retrospective analysis was performed for the clinical data of 85 patients with hepatocellular carcinoma( HCC) who underwent TACE in The First Affiliated Hospital of Soochow University from October 2016 to March 2018. The serum levels of AFP and DCP were measured before TACE and after two consecutive sessions of TACE,and modified RECIST( mRECIST) was used to evaluate the therapeutic effect of TACE. The changes in AFP and DCP were compared with imaging findings based on mRECIST. The two-independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The chi-square test was used for comparison of categorical data between two groups,and the Mann-Whitney U test was used for comparison of ranked data between two groups. A Spearman correlation analysis was used to investigate the correlation of mRECIST category with AFP and DCP. The receiver operating characteristic( ROC) curve was used to investigate the value of each index in the diagnosis of remission. Results According to the mRECIST criteria,38 patients achieved remission( remission group) and 31 did not achieve remission( non-remission group). After treatment,the remission group had significantly lower AFP and DCP than the non-remission group( Z =-3. 366 and-4. 065,both P < 0. 05). There were significant differences between the remission group and the non-remission group inΔAFP,ΔDCP,ΔAFP%,and ΔDCP%( Z =-4. 837,-5. 597,-4. 210,and-5. 851,all P < 0. 001). The mRECIST category was negatively correlated with ΔAFP and ΔDCP( rs=-0. 552 and-0. 593,both P < 0. 001). In the diagnosis of remission,ΔAFP% had an area under the ROC curve( AUC) of 0. 796,while ΔDCP% had an AUC of 0. 912 and ΔAFP% combined with ΔDCP% had an AUC of0. 921,suggesting that ΔAFP% combined with ΔDCP% had the highest diagnostic value. Conclusion Changes in serum DCP and AFP after TACE can be used to evaluate the outcome of HCC after TACE.
Objective To investigate the value of alpha-fetoprotein( AFP) combined with des-γ-carboxy-prothrombin( DCP) in predicting the therapeutic effect of transarterial chemoembolization( TACE). Methods A retrospective analysis was performed for the clinical data of 85 patients with hepatocellular carcinoma( HCC) who underwent TACE in The First Affiliated Hospital of Soochow University from October 2016 to March 2018. The serum levels of AFP and DCP were measured before TACE and after two consecutive sessions of TACE,and modified RECIST( mRECIST) was used to evaluate the therapeutic effect of TACE. The changes in AFP and DCP were compared with imaging findings based on mRECIST. The two-independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The chi-square test was used for comparison of categorical data between two groups,and the Mann-Whitney U test was used for comparison of ranked data between two groups. A Spearman correlation analysis was used to investigate the correlation of mRECIST category with AFP and DCP. The receiver operating characteristic( ROC) curve was used to investigate the value of each index in the diagnosis of remission. Results According to the mRECIST criteria,38 patients achieved remission( remission group) and 31 did not achieve remission( non-remission group). After treatment,the remission group had significantly lower AFP and DCP than the non-remission group( Z =-3. 366 and-4. 065,both P < 0. 05). There were significant differences between the remission group and the non-remission group inΔAFP,ΔDCP,ΔAFP%,and ΔDCP%( Z =-4. 837,-5. 597,-4. 210,and-5. 851,all P < 0. 001). The mRECIST category was negatively correlated with ΔAFP and ΔDCP( rs=-0. 552 and-0. 593,both P < 0. 001). In the diagnosis of remission,ΔAFP% had an area under the ROC curve( AUC) of 0. 796,while ΔDCP% had an AUC of 0. 912 and ΔAFP% combined with ΔDCP% had an AUC of0. 921,suggesting that ΔAFP% combined with ΔDCP% had the highest diagnostic value. Conclusion Changes in serum DCP and AFP after TACE can be used to evaluate the outcome of HCC after TACE.
引文
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[14]ZHENG HL,ZHAO R,LI DP,et al.The significance of the level changes of serum DCP and AFP before and after the intervention treatment in patients with primary hepatic carcinoma[J].Acta Acad Med Bengbu,2014,39(8):1012-1014.(in Chinese)郑海伦,赵睿,李大鹏,等.原发性肝癌患者介入治疗前后血清异常凝血酶原和甲胎蛋白变化的意义[J].蚌埠医学院学报,2014,39(8):1012-1014.
[15]ZHANG QL,XING XZ,ZHANG LY,et al.Clinical value of combined detection of pokemon,AFP-L3,AFP and DCP after transarterial chemoembolization for hepatocellular carcinoma[J].Anhui Med Pharm J,2017,21(3):468-471.(in Chinese)张全乐,邢喜芝,张立英,等.肝癌介入治疗前后原癌基因Pokemon、甲胎蛋白异质体、甲胎蛋白、脱γ-羧基凝血酶原联合检测的临床价值[J].安徽医药,2017,21(3):468-471.
[16]ICHIKAWA T,MACHIDA N,SASAKI H,et al.Early prediction of the outcome using tumor markers and mRECIST in unresectable hepatocellular carcinoma patients who underwent transartery chemoembolization[J].Oncology,2016,91(6):317-330.
[17]ARAI T,KOBAYASHI A,OHYA A,et al.Assessment of treatment outcomes based on tumor marker trends in patients with recurrent hepatocellular carcinoma undergoing trans-catheter arterial chemo-embolization[J].Int J Clin Oncol,2014,19(5):871-879.
[18]PARK WH,SHIM JH,HAN SB,et al.Clinical utility of des-γ-car-boxy prothrombin kinetics as a complement to radiologic response in patients with hepatocellular carcinoma undergoing transarterial chemoembolization[J].J Vasc Interv Radiol,2012,23(7):927-936.
[19]ZHAO CH,ZHOU WF,CHEN WH,et al.Clinical significance ofα-fetoprotein in initial diagnosis of primary hepatic cancer?[J].J Clin Hepatol,2013,29(9):698-701.(in Chinese)赵春华,周文峰,陈维华,等.甲胎蛋白在原发性肝癌首诊中的价值[J].临床肝胆病杂志,2013,29(9):698-701.
[20]HU B,TIAN X,SUN J.Evaluation of individual and combined applications of serum biomarkers for diagnosis of hepatocellular carcinoma:A meta-analysis[J].Int J Mol Sci,2013,14(12):23559-23580.
[21]WU B,ZHOU J,LING G,et al.Calli Spheres drug-eluting beads versus lipiodol transarterial chemoembolization in the treatment of hepatocellular carcinoma:A short-term efficacy and safety study[J].World J Surg Oncol,2018,16(1):69.
[2]RAOUL JL,SANGRO B,FORNER A,et al.Evolving strategies for the management of intermediate-ate-stage hepatocellular carcinoma:Available evidence and expert opinion on the use of transarterial chemoembolization[J].Cancer Treat Rev,2011,37(3):212-220.
[3]LIANG YF,SHI L,SUN NN,et al.Analysis of the dynamic changes and clinic significance of serum CA724,CA242 and AFP levels before and after TACE treatment of primary hepatic carcinoma[J].Tianjin Med J,2015,43(10):1183-1186.(in Chinese)梁育飞,石亮,孙宁宁,等.CA724、CA242及AFP在肝癌TA-CE治疗前后的表达变化及临床意义[J].天津医药,2015,43(10):1183-1186.
[4]CUI HZ,WANG MC,XU AF,et al.Correlation analysis of alpha fetoprotein changes and therapeutic effect after transcatheter arterial chemoembolization[J].Chin J Health Lab Technol,2018,28(10):1220-1222.(in Chinese)崔怀中,王妙婵,徐爱芳,等.肝动脉栓塞化疗术后甲胎蛋白变化与疗效的相关性分析[J].中国卫生检验杂志,2018,28(10):1220-1222.
[5]LIN YY,CHEN Y,CHEN YS,et al.Clinical value of the abnormal prothrombin PVKIA-Ⅱin detection of hepatocellular carcinoma[J].Curr Immunol,2015,35(4):328-333.(in Chinese)林莺莺,陈燕,陈岩松,等.异常凝血酶原(PIVKA-Ⅱ)检测在肝细胞癌中的临床价值[J].现代免疫学,2015,35(4):328-333.
[6]National Health and Family Planning Commission of the People's Republic of China.Diagnosis,management,and treatment of hepatocellular carcinoma(V2017)[J].J Clin Hepatol,2017,33(8):1419-1431.(in Chinese).中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范(2017年版)[J].临床肝胆病杂志,2017,33(8):1419-1431.
[7]OKEN MM,CREECH RH,TORMEY DC,et al.Toxicity and response criteria of the eastern cooperative oncology group[J].Am J Clin Oncol,1982,5(6):649-655.
[8]LENCIONI R,LLOVET JM.Modified RECIST(mRECIST)assessment for hepatocellular carcinoma[J].Semin Liver Dis,2010,30(1):52-60.
[9]SUN ZD,CHENG LM,PING P,et al.Analysis of the risk factors for prognosis of surgical treatment patients with primary liver cancer[J].J Clin Exp Med,2017,16(12):1204-1207.(in Chinese)孙志德,程利民,平萍,等.影响原发性肝癌患者手术治疗预后的危险因素分析[J].临床和实验医学杂志,2017,16(12):1204-1207.
[10]XIA DD,WANG EX,WANG WJ,et al.Early alpha-fetoprotein response can predict the prognosis of patients with intermediate-stage hepatocellular carcinoma trated with transarterial chemoembolization[J].J Clin Hepatol,2017,33(6):1120-1125.(in Chinese)夏冬东,王恩鑫,王文军,等.早期AFP应答对经肝动脉化疗栓塞术后中期肝细胞癌患者预后的预测价值[J].临床肝胆病杂志,2017,33(6):1120-1125.
[11]ZHENG HL,ZHAO R,LI DP,et al.Utility of DCP and AFP in diagnosis of primary liver cancer[J].Chin J Gen Prac,2016,14(1):29-31.(in Chinese)郑海伦,赵睿,李大鹏,等.肿瘤标志物DCP和AFP在原发性肝癌中的诊断价值[J].中华全科医学,2016,14(1):29-31.
[12]LIEBMAN HA,FURIE BC,TONG MJ,et al.Des-g-carboxy(abnormal)prothrombin as a serum marker of primary hepatocellular carcinoma[J].N Engl J Med,1984,310(22):1427-1431.
[13]WANG QS.Application of serum abnormal prothrombin and alpha-fetoprotein in the diagnosis of primary hepatic carcinoma[J].J Shenyang Med Coll,2017,19(4):336-338.(in Chinese)王全胜.血清异常凝血酶原和甲胎蛋白在原发性肝癌诊断中的应用[J].沈阳医学院学报,2017,19(4):336-338.
[14]ZHENG HL,ZHAO R,LI DP,et al.The significance of the level changes of serum DCP and AFP before and after the intervention treatment in patients with primary hepatic carcinoma[J].Acta Acad Med Bengbu,2014,39(8):1012-1014.(in Chinese)郑海伦,赵睿,李大鹏,等.原发性肝癌患者介入治疗前后血清异常凝血酶原和甲胎蛋白变化的意义[J].蚌埠医学院学报,2014,39(8):1012-1014.
[15]ZHANG QL,XING XZ,ZHANG LY,et al.Clinical value of combined detection of pokemon,AFP-L3,AFP and DCP after transarterial chemoembolization for hepatocellular carcinoma[J].Anhui Med Pharm J,2017,21(3):468-471.(in Chinese)张全乐,邢喜芝,张立英,等.肝癌介入治疗前后原癌基因Pokemon、甲胎蛋白异质体、甲胎蛋白、脱γ-羧基凝血酶原联合检测的临床价值[J].安徽医药,2017,21(3):468-471.
[16]ICHIKAWA T,MACHIDA N,SASAKI H,et al.Early prediction of the outcome using tumor markers and mRECIST in unresectable hepatocellular carcinoma patients who underwent transartery chemoembolization[J].Oncology,2016,91(6):317-330.
[17]ARAI T,KOBAYASHI A,OHYA A,et al.Assessment of treatment outcomes based on tumor marker trends in patients with recurrent hepatocellular carcinoma undergoing trans-catheter arterial chemo-embolization[J].Int J Clin Oncol,2014,19(5):871-879.
[18]PARK WH,SHIM JH,HAN SB,et al.Clinical utility of des-γ-car-boxy prothrombin kinetics as a complement to radiologic response in patients with hepatocellular carcinoma undergoing transarterial chemoembolization[J].J Vasc Interv Radiol,2012,23(7):927-936.
[19]ZHAO CH,ZHOU WF,CHEN WH,et al.Clinical significance ofα-fetoprotein in initial diagnosis of primary hepatic cancer?[J].J Clin Hepatol,2013,29(9):698-701.(in Chinese)赵春华,周文峰,陈维华,等.甲胎蛋白在原发性肝癌首诊中的价值[J].临床肝胆病杂志,2013,29(9):698-701.
[20]HU B,TIAN X,SUN J.Evaluation of individual and combined applications of serum biomarkers for diagnosis of hepatocellular carcinoma:A meta-analysis[J].Int J Mol Sci,2013,14(12):23559-23580.
[21]WU B,ZHOU J,LING G,et al.Calli Spheres drug-eluting beads versus lipiodol transarterial chemoembolization in the treatment of hepatocellular carcinoma:A short-term efficacy and safety study[J].World J Surg Oncol,2018,16(1):69.