Value of combined determination of hepatitis C virus genotype,AFP-L3,and P53 antibody in the diagnosis of hepatitis C virus-related hepatocellular carcinoma
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摘要: 目的探讨HCV基因分型、甲胎蛋白异质体(AFP-L3)和P53抗体联合检测在HCV相关肝细胞癌(HCV-HCC)中的诊断价值。方法选取2016年1月-2019年12月在绵阳市第三人民医院确诊的HCV-HCC患者84例及良性肝病对照组(丙型肝炎患者、HCV肝硬化患者) 84例。分别采用PCR-反向点杂交技术、ELISA方法、电化学发光法检测HCV基因分型、P53抗体、AFP-L3。计量资料组间比较采用t检验和Kruskal-Wallis H检验;计数资料组间比较采用χ2检验。通过logistic回归分析和受试者工作特征曲线(ROC曲线)比较各指标对HCV-HCC的诊断价值。结果 HCV-HCC组HCV 1b基因型(%)、AFP-L3(%)、P53抗体明显高于良性肝病对照组(χ2=5.714、Z=-9.27、Z=-9.92,P值均<0.05)。logistic回归分析结果显示,HCV基因分型、AFP-L3(%)、P53抗体对HCV-HCC的影响均有统计学意义(P值均<0.05)。将上述单项指标重新拟合并建立模型:Logit(Y)=-3...Abstract: Objective To investigate the value of combined determination of hepatitis C virus( HCV) genotype,the alpha-fetoprotein variant AFP-L3,and P53 antibody in HCV-related hepatocellular carcinoma( HCV-HCC). Methods A total of 84 patients with HCV-HCC who were diagnosed in our hospital from January 2016 to December 2019 were enrolled as HCV-HCC group,and 84 patients with benign liver diseases( hepatitis C and HCV liver cirrhosis) were enrolled as control group. The PCR-reverse dot blot hybridization technique was used to determine HCV genotype,ELISA was used to measure P53 antibody,and electrochemical luminescence was used to measure AFP-L3. The t-test and the Kruskal-Wallis H test were used for comparison between two groups; the chi-square test was used for comparison of categorical data between two groups. The logistic regression analysis and the receiver operating characteristic( ROC) curve were used to compare the value of each index in the diagnosis of HCV-HCC. Results Compared with the control group,the HCV-HCC group had a significantly higher proportion of patients with HCV 1 b genotype or AFP-L3 and a significantly higher level of P53 antibody( χ2=5. 714,Z =-9. 27,Z =-9. 92,all P < 0. 05). The logistic regression analysis showed that HCV genotype,AFP-L3,and P53 antibody had significant effects on HCV-HCC( all P < 0. 05). The above indices were fitted to establish a model of Logit( Y) =-3. 881 +0. 031 X(AFP-L3( %))+ 0. 043 XP53+ 1. 218 X(HCV genotype),in which Y was the positive probability value of combined determination. In the screening of HCV-HCC,Y had a significantly larger area under the ROC curve than HCV genotype( 0. 945 vs 0. 758,Z = 6. 17,P < 0. 001),AFP-L3( 0. 945 vs 0. 863,Z = 3. 97,P < 0. 001),and P53 antibody( 0. 945 vs 0. 887,Z = 3. 07,P = 0. 002). Y had higher AUC( 0.945),sensitivity( 90. 90%),specificity( 94. 00%),positive predictive value( 93. 80%),negative predictive value( 91. 16%),and diagnostic accuracy( 92. 44%) than each index alone. Conclusion HCV 1 b genotype,AFP-L3,and P53 antibody level are associated with the risk of HCV-HCC,and the combined determination of the three indices has important clinical significance in the early diagnosis of HCV-HCC.
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Key words:
- hepacivirus /
- carcinoma,hepatocellular /
- genotype /
- alpha-fetoproteins /
- tumor suppressor protein p53 /
- early diagnosis
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[1] MOROZOV VA,LAGAYE S. Hepatitis C virus:Morphogenesis,infection and therapy[J]. World J Hepatol,2018,10(2):186-212. [2] WHO. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection[M]. Geneva:Word Health Organization,2018. [3] Expert Panel of Antiviral Therapy for Hepatocellular Carcinoma.Expert consensus on antiviral therapy to hepatitis B/C virusrelated hepatocellular carcinoma[J]. J Clin Hepatol,2014,30(5):390-395.(in Chinese)肝细胞癌抗病毒治疗专家组.HBV/HCV相关性肝细胞癌抗病毒治疗专家共识[J].临床肝胆病杂志,2014,30(5):390-395. [4] LI B,LI BA. The significance of autoantibodies detection for the diagnosis of primary hepatic carcinoma[J]. Chin J Lab Med,2016,39(2):76-78.(in Chinese)李波,李伯安.自身抗体检测在原发性肝癌诊断中的意义[J].中华检验医学杂志,2016,39(2):76-78. [5] Bureau of Medical Administration,National Health Commission of the People’s Republic of China. Guidelines for diagnosis and treatment of primary liver cancer in China(2019 edition)[J]. J Clin Hepatol,2020,36(2):277-292.(in Chinese)中华人民共和国国家卫生健康委员会医政医管局.原发性肝癌诊疗规范(2019年版)[J].临床肝胆病杂志,2020,36(2):277-292. [6] XIE F,YU YC,XUE Z,et al. Screening strategy for primary hepatocellular carcinoma based on different combinations of protein induced by vitamin K absence or antagonist-II,alpha-fetoprotein,and alpha-fetoprotein-L3[J]. J Clin Hepatol,2019,35(9):1975-1979.(in Chinese)谢芳,于乐成,薛珠,等.基于PIVKA-Ⅱ、AFP和AFP-L3不同组合模式的肝细胞癌筛查策略探讨[J].临床肝胆病杂志,2019,35(9):1975-1979. [7] GUAN GW,YAO MJ,QIAN XJ,et al. Value of combined measurement of alpha-fetoprotein and alpha-fetoprotein L3%in the diagnosis of hepatocellular carcinoma[J]. J Clin Hepatol,2019,35(7):1514-1519.(in Chinese)关贵文,姚明解,钱相君,等.AFP和AFP-L3%联合检测在肝细胞癌诊断中的应用价值[J].临床肝胆病杂志,2019,35(7):1514-1519. [8] CAO YL,SHAN J,GONG ZZ,et al. Interpretation of the TRIPOD statement:A reporting guideline for multivariable prediction model for individual prognosis or diagnosis[J]. Chin J Evid-based Med,2020,20(4):492-496.(in Chinese)曹煜隆,单娇,龚志忠,等.个体预后与诊断预测模型研究报告规范———TRIPOD声明解读[J].中国循证医学杂志,2020,20(4):492-496. [9] National Health and Family Planning Commission of The People’s Republic of China. WS 213-2018 Diagnosis for hepatitis C[J]. J Clin Hepatol,2018,34(8):1619-1621.(in Chinese)中华人民共和国国家卫生和计划生育委员会.WS 213—2018丙型肝炎诊断[J].临床肝胆病杂志,2018,34(8):1619-1621. [10] Bureau of Medical Administration,National Health and Family Planning Comission 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)中华人民共和国卫生和计划生育委员会医政医管局.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. [11] OBUCHOWSKI NA,MCCLISH DK. Sample size determination for diagnostic accuracy studies involving binormal ROC curve indices[J]. Stat Med,1997,16(13):1529-1542. [12] ZHOU M,WANG H,ZENG X,et al. Mortality,morbidity,and risk factors in China and its provinces,1990-2017:A systematic analysis for the Global Burden of Disease Study 2017[J].Lancet,2019,394(10204):1145-1158. [13] KOZIOL JA,IMAI H,DAI L,et al. Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens[J]. Cancer Immunol Immunother,2018,67(5):835-841. [14] LEE MH,YANG HI,LU SN,et al. Hepatitis C virus genotype1b increases cumulative lifetime risk of hepatocellular carcinoma[J]. Int J Cancer,2014,135(5):1119-1126. [15] BUSATO D,MOSSENTA M,BABOCI L,et al. Novel immunotherapeutic approaches for hepatocellular carcinoma treatment[J]. Expert Rev Clin Pharmacol,2019,12(5):453-470. [16] HWANG HM,HEO CK,LEE HJ,et al. Identification of antiSF3B1 autoantibody as a diagnostic marker in patients with hepatocellular carcinoma[J]. J Transl Med,2018,16(1):177. [17] MA H,SUN X,CHEN L,et al. Multiplex immunochips for highaccuracy detection of AFP-L3%based on surface-enhanced raman scattering:Implications for early liver cancer diagnosis[J]. Anal Chem,2017,89(17):8877-8883. [18] YU R,TAN Z,XIANG X,et al. Effectiveness of PIVKA-II in the detection of hepatocellular carcinoma based on realworld clinical data[J]. BMC Cancer,2017,17(1):608. 期刊类型引用(16)
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