ImCare Biotech LLC, Doylestown, Pennsylvania, USA.
Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Clin Transl Gastroenterol. 2020 Dec;11(12):e00271. doi: 10.14309/ctg.0000000000000271.
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.
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 在检测肝硬化、乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）患者 HCC 中的表现，包括其早期阶段。
我们进行了一项盲法、前瞻性病例对照研究，纳入了 488 名患者，包括 164 名 HCC 患者（81 名早期 HCC）和 324 名对照。通过酶联免疫吸附测定（ELISA）检测血清 LC-SPIK 水平。比较血清 LC-SPIK 和甲胎蛋白（AFP）的表现，包括曲线下面积（AUC）、敏感性和特异性。在 102 名患者的独立验证队列中评估了 LC-SPIK 的性能。
在将所有 HCC 患者与肝硬化和慢性 HBV/HCV 患者区分开来时，LC-SPIK 的 AUC 为 0.87，使用 21.5ng/mL 的截断值时，其敏感性为 80%，特异性为 90%。这明显高于 AFP，使用标准截断值 20.0ng/mL 时，其 AUC 为 0.70，敏感性为 52%，特异性为 86%。对于早期 HCC（巴塞罗那临床肝癌分期 0 和 A），LC-SPIK 的 AUC 为 0.85，敏感性为 72%，特异性为 90%，而 AFP 的 AUC 为 0.61，敏感性为 42%，特异性为 86%。此外，LC-SPIK 能够准确检测出 AFP 结果为阴性的 HCC 患者中超过 70%的 HCC 存在。
该研究提供了强有力的证据表明，LC-SPIK 以高灵敏度和特异性检测 HCC，包括早期 HCC，并且可能对肝硬化和慢性 HBV/HCV 患者的监测有用，这些患者患 HCC 的风险较高。
