Liver Cancer-Specific Serine Protease Inhibitor Kazal Is a Potentially Novel Biomarker for the Early Detection of Hepatocellular Carcinoma.
Liver Cancer-Specific Serine Protease Inhibitor Kazal Is a Potentially Novel Biomarker for the Early Detection of Hepatocellular Carcinoma.
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DOI：
10.14309/ctg.0000000000000271
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发表时间：
2020-12
影响因子：
3.6
通讯作者：
Lu X
中科院分区：
文献类型：
--
作者：
Lu F;Shah PA;Rao A;Gifford-Hollingsworth C;Chen A;Trey G;Soryal M;Talat A;Aslam A;Nasir B;Choudhry S;Ishtiaq R;Sanoff H;Conteh LF;Noonan A;Hu KQ;Schmidt C;Fu M;Civan J;Xiao G;Lau DT;Lu X
肝癌分泌的丝氨酸蛋白酶抑制剂Kazal（LC-SPIK）是一种在肝细胞癌（HCC）病例中特异性升高的蛋白质。我们评估了LC-SPIK在肝硬化、B型肝炎病毒（HBV）和丙型肝炎病毒（HCV）患者中检测HCC（包括早期）的性能。我们在一项盲法、前瞻性、病例对照研究中招募了488名患者，包括164名HCC患者（81名早期HCC）和324名对照。血清LC-SPIK水平通过酶联免疫吸附测定法测定。比较血清LC-SPIK和甲胎蛋白（AFP）的性能，包括曲线下面积（AUC）、灵敏度和特异性。在一个包含102名患者的独立验证队列中评价了LC-SPIK的性能。在区分所有HCC患者与肝硬化和慢性HBV/HCV患者时，LC-SPIK的AUC为0.87，敏感性为80%，特异性为90%，临界值为21.5 ng/mL。这显著高于AFP，其具有0.70的AUC和52%的灵敏度和86%的特异性，使用20.0 ng/mL的标准截止值。对于早期HCC（巴塞罗那临床肝癌0期和A期），LC-SPIK的AUC为0.85，灵敏度为72%，特异性为90%，而AFP的AUC为0.61，灵敏度为42%，特异性为86%。此外，LC-SPIK在超过70%的AFP结果为假阴性的HCC患者中准确检测到HCC的存在。该研究提供了强有力的证据表明，LC-SPIK检测HCC，包括早期HCC，具有高灵敏度和特异性，可能有助于监测处于HCC高风险中的慢性HBV/HCV患者。
Liver cancer–secreted serine protease inhibitor Kazal (LC-SPIK) is a protein that is specifically elevated in cases of hepatocellular carcinoma (HCC). We assessed the performance of LC-SPIK in detecting HCC, including its early stages, in patients with cirrhosis, hepatitis B virus (HBV), and hepatitis C virus (HCV). We enrolled 488 patients, including 164 HCC patients (81 early HCC) and 324 controls in a blinded, prospective, case–control study. Serum LC-SPIK levels were determined by an enzyme-linked immunosorbent assay-based assay. The performance of serum LC-SPIK and α-fetoprotein (AFP), including area under the curve (AUC), sensitivity, and specificity, are compared. The performance of LC-SPIK was evaluated in an independent validation cohort with 102 patients. In distinguishing all HCC patients from those with cirrhosis and chronic HBV/HCV, LC-SPIK had an AUC of 0.87, with 80% sensitivity and 90% specificity using a cutoff of 21.5 ng/mL. This is significantly higher than AFP, which had an AUC of 0.70 and 52% sensitivity and 86% specificity using a standard cutoff value of 20.0 ng/mL. For early-stage HCC (Barcelona Clinic Liver Cancer stage 0 and A), LC-SPIK had an AUC of 0.85, with 72% sensitivity and 90% specificity, compared with AFP, which had an AUC of 0.61, with 42% sensitivity and 86% specificity. In addition, LC-SPIK accurately detected the presence of HCC in more than 70% of HCC patients with false-negative AFP results. The study provided strong evidence that LC-SPIK detects HCC, including early-stage HCC, with high sensitivity and specificity, and might be useful for surveillance in cirrhotic and chronic HBV/HCV patients, who are at an elevated risk of developing HCC.
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