1. Liver Cancer–Specific Serine Protease Inhibitor Kazal Is a Potentially Novel Biomarker for the Early Detection of Hepatocellular Carcinoma
- Author
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Lu, Felix, Shah, Ahmad, Rao, Abhishek, Gifford-Hollingsworth, Cynthia, Chen, Anne, Trey, Gary, Soryal, Mina, Talat, Arslan, Aslam, Aysha, Nasir, Bilal, Choudhry, Saad, Ishtiaq, Rizwan, Sanoff, Hanna, Conteh, Lanla F, Noonan, Anne, Hu, Ke-Qin, Schmidt, Carl, Fu, Min, Civan, Jesse, Xiao, Gary, Lau, Daryl T-Y, and Lu, Xuanyong
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Prevention ,Hepatitis - B ,Clinical Research ,Infectious Diseases ,Liver Disease ,Rare Diseases ,Hepatitis ,Digestive Diseases ,Liver Cancer ,Hepatitis - C ,HIV/AIDS ,Cancer ,Emerging Infectious Diseases ,Chronic Liver Disease and Cirrhosis ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Infection ,Good Health and Well Being ,Adult ,Biomarkers ,Tumor ,Biopsy ,Carcinoma ,Hepatocellular ,Case-Control Studies ,Early Detection of Cancer ,Female ,Humans ,Liver ,Liver Neoplasms ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Prospective Studies ,Protein Isoforms ,ROC Curve ,Tomography ,X-Ray Computed ,Trypsin Inhibitor ,Kazal Pancreatic ,Clinical sciences - Abstract
IntroductionLiver 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).MethodsWe 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.ResultsIn 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.DiscussionThe 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.
- Published
- 2020