摘要
目的探讨血清异常凝血酶原（PIVKA-Ⅱ）和甲胎蛋白（AFP）在原发性肝癌（HCC）诊断和疗效监测中的价值。方法病例对照研究。用化学发光法和电化学发光法检测2013年8月至2014年3月期间青岛大学附属医院148例肝细胞癌、37例肝内胆管细胞癌、44例胃、结直肠癌、63例肝硬化、38例慢性乙型肝炎、57例体检健康者血清PIVKA—Ⅱ和AFP水平，分别分析两者单独及联合检测诊断HCC的受试者工作曲线下面积（ROC—AUC）、敏感度和特异性；分析血清PIVKA—Ⅱ和AFP水平与肿瘤直径大小及TNM分期的相关性；比较HCC患者治疗前后两指标血清水平的变化。结果肝细胞癌组血清PIVKA一1I和AFP水平均高于肝内胆管细胞癌组、胃结直肠癌组、肝硬化组、慢性乙型肝炎组和健康对照组（PIVKA—Ⅱ：U值分别为866．50、424．00、958．00、292．00和448．00；AFP：U值分别为713．00、440．50、1182．00、614．00和399．00，P均〈0．001）。两指标单独检测和联合检测对HCC组患者的ROC—AUC均差异无统计学意义（P〉0．05）。PIVKA-Ⅱ诊断HCC的敏感度（87．16％）高于AFP（68．92％，=4．73，P〈0．05），PIVKA—Ⅱ和AFP联合检测诊断HCC的敏感度（93．24％）高于PIVKA—Ⅱ单项检测（87．16％，校正x^2=64．70，P〈0．01），但特异度之间比较差异均无统计学意义（P〉0．05）。Spearman秩相关分析显示，血清PIVKA-Ⅱ和AFP水平与肿瘤大小均呈正相关（相关系数分别为0．716和0．475，P均〈0．001）。随肿瘤直径增大，HCC患者PIVKA—Ⅱ和AFP水平逐渐升高（日值分别为72．70、37．02，P均〈0．001）；阳性率也逐渐提高（x^2值分别为26．74、21．62，P均〈0．001）。按国际肿瘤TNM分期，Ⅰ～Ⅳ期血清PIVKA-Ⅱ和AFP水平（H值分别为46．63、21．38，P均〈0．001）与阳性率（PIVKA—Ⅱ：X2=20．40，P〈0．01；AFP：X2=8．33，P〈0．05）也随TNM肿瘤分期的增高而升高。HCC患者治疗后血清PIVKA．U和AFP水平均低于治疗前（z值分别为-4．59、-4．22，P均〈0．001），不同TNM分期患者治疗后PIVKA-Ⅱ（z值分别为-2．85、-2．98、-2．70，P均〈0．05）和AFP水平均分别低于同期治疗前水平（z值分别为-2．48、-3．82、-2．50，P均〈0．05）。结论血清PIVKA—Ⅱ和AFP对HCC诊断和疗效监测均具有较高的临床应用价值，PIVKA-Ⅱ诊断HCC的敏感度明显高于AFP，两者联合检测可提高单独检测的敏感度，而不降低其特异度。r中华检验医学杂志．2014，37：928．932、
Objective To discuss the clinical value of Protein induced by Vitamin K Antagonist-Ⅱ （PIVKA-lI ） and alpha-Fetoproteins （AFP） in diagnosing hepatocellular carcinoma （HCC） and monitoring the treatment effects. Methods Patients were recruited by the Affiliated Hospital of Qingdao University, from August 2013 to March 2014. Serum levels of PIVKA-Ⅱ and AFP were measured by both chemiluminescence assay （CLIA） and electrochemiluminescencc assay （ECLA） in patients with HCC （n = 148 ）, intrahepatic cholangioceUular carcinoma （ n = 37 ）, gastric cancer and colorectal cancer （ n = 44）, cirrhosis （ n = 63 ）, chronic hepatitis B （n = 38） and healthy subjects （n = 57）. To analyze the areas under the receiver operating characteristic curves （ROC-AUC） and to compare the sensitivity and specificity ofsingle PIVKA- U or AFP assay, and the combined detection. To analyze the correlation of PIVKA- Ⅱand both tumor size and TNM staging, so do AFP, respectively. To compare the serum level changes of the two indicators in HCC patients before and after treatment. Results The serum levels of both PIYKA-Ⅱ and AFP in HCC group were higher than that in intrahepatic cholangiocellular carcinoma, gastric cancer and colorectal cancer, cirrhosis, chronic hepatitis B and healthy subjects groups （ PIVKA- Ⅱ ： U = 866. 50, 424. 00, 958.00, 292.00 and 448.00 ; AFP：U=713.00, 440.50, 1 182.00, 614.00 and 399.00, P〈0. 001） . The ROC-AUCs of the single PIVKA- II or AFP assay and the combined detection in HCC group were not statistically different （ P 〉 0. 05 ） . The sensitivity of PIVKA- Ⅱ （ 87. 16% ） was higher than that of AFP （68.92% ,X2 =4. 73 ,P 〈 0. 05）in diagnosing HCC; the sensitivity of the combined detection of PIVKA-I1 and AFP （93.24%） was higher than that of PIVKA- Ⅱ itself （ 87.16%, adjusted X2 = 64. 70, P 〈 0. 01 ） ; while the specificities among them did not show statistical significance （P 〉 0. 05）. Tested by Spearman rank correlation, the serum levels of PIVKA- Ⅱ and AFP were both positively related to tumor size （ r = 0. 716, 0. 475 respectively, P 〈 0. 001 ）. The serum levels of PIVKA- Ⅱ and AFP in HCC patients increased gradually correlated with tumor size （H = 72. 70, 37.02 respectively, P 〈 0. 001 ） and the positive rates of PIVKA- Ⅱ and AFP were gradually improved （ X2 = 26. 74, 21.62 respectively, P 〈 0. 01 ）, too. Based on the International TNM Staging System, the serum levels of PIVKA- Ⅱ and AFP （ H = 46.63, 21.38 respectively, P 〈 0. 001 ） and the positive rates of PIVKA-Ⅱand AFP （ PIVKA- Ⅱ ： X2 = 20.40, P 〈 0.01 ; AFP： X2 = 8.33 ,P 〈0.05） in HCC patients from Ⅰ -IV stages were increased as TNM stages elevated. The serum levels of PIVKA- Ⅱ and AFP in HCC patients were both dropped sharply compared with preoperative levels （Z = -4. 59, -4. 22 respectively, P 〈 0. 001 ） and also both dropped in each of theⅠ-Ⅳ TNM stages （ PIVKA- II ： Z = - 2. 85, - 2.98, - 2. 70 respectively, P 〈 O. 05 ; AFP ： Z = - 2. 48, - 3.82, - 2. 50 respectively, P 〈 0. 05） compared with serum levels before treatment. Conclusion PIVKA-Ⅱ and AFP both have high clinical application values in diagnosing HCC and monitoring treatment effects. The sensitivity of PIVKA-Ⅱ in diagnosing HCC is significantly higher than AFP, and the sensitivity can be elevated by the combined detection in diagnosing HCC without reducing the specificity. （Chin J Lab Med,2014,37：928-932）
出处
《中华检验医学杂志》
CAS
CSCD
北大核心
2014年第12期928-932,共5页
Chinese Journal of Laboratory Medicine
关键词
癌
肝细胞
蛋白质前体
凝血酶原
生物学标记
甲胎蛋白类
Carcinoma, hepatocellular
Protein precursors
Prothrombin
Biologicalmarkers
Alpha-Fetoproteins
