Human liver carboxylesterase 1 outperforms alpha‐fetoprotein as biomarker to discriminate hepatocellular carcinoma from other liver diseases in Korean patients

• Published in: International journal of cancer Vol. 133; no. 2; pp. 408 - 415
• Main Authors: Na, Keun, Jeong, Seul‐Ki, Lee, Min Jung, Cho, Sang Yun, Kim, Sun A, Lee, Min‐Ji, Song, Si Young, Kim, Hoguen, Kim, Kyung Sik, Lee, Hyun Woong, Paik, Young‐Ki
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 15.07.2013; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; alpha-Fetoproteins - metabolism; alpha‐fetoprotein; Antibodies, Monoclonal; Area Under Curve; Biological and medical sciences; biomarker; Biomarkers; Biomarkers, Tumor - metabolism; Cancer; Carboxylic Ester Hydrolases - genetics; Carboxylic Ester Hydrolases - metabolism; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - diagnosis; Cohort Studies; Female; Gastroenterology. Liver. Pancreas. Abdomen; hepatocellular carcinoma; Humans; Liver cancer; liver carboxylesterase 1; Liver cirrhosis; Liver diseases; Liver Diseases - blood; Liver Diseases - diagnosis; Liver Neoplasms - blood; Liver Neoplasms - diagnosis; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Proteomics; ROC Curve; Sensitivity and Specificity; Tropical medicine; Tumors; Asia; Korea; Human; Enzyme; Biological marker; Hepatic disease; Hepatocellular carcinoma; Esterases; Malignant tumor; alpha-fetoprotein; Carboxylesterase; α-Fetoprotein; biomarker; Carboxylic ester hydrolases; Liver cancer; Cancerology; Hydrolases; Digestive diseases; Diagnosis; liver carboxylesterase 1; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.28020

Although alpha‐fetoprotein (AFP) is currently the major serologic biomarker for hepatocellular carcinoma (HCC), it cannot efficiently distinguish this cancer from other forms of liver disease in early diagnosis due to its low sensitivity. The aim of this study is to compare sensitivity and specificity of human carboxylesterase 1 (hCE1) and AFP biomarker. Antibody‐based assays for hCE1 and AFP were used to test both biomarkers with respect to diagnostic efficiency, Youden's index and the area under the curve (AUC) through receiver operating characteristic (ROC) analysis in plasma from 208 patients with HCC (n=57), liver cirrhosis (n=27), chronic hepatitis (n=37), cholangiocarcinoma (n=22), gastric cancer (n=31) and pancreatic cancer (n=34), along with 52 healthy donors (HDs). The levels of hCE1 were significantly higher in patients with HCC than HDs and the other diseases (p<0.005), further verified by AUC values and Youden's index. In the set of HCC versus liver cirrhosis the AUC values were 0.744 (AFP), 0.918 (hCE1) and 0.938 (combination of AFP and hCE1), respectively. These results indicate that hCE1 is not only a more potent and specific marker in distinguishing cancer from liver diseases, in particular cirrhosis, but the combination of hCE1 and AFP shows also synergistic potential for greater sensitivity and specificity in early diagnosis. Therefore the antibody‐based hCE1 assay appears to have high diagnostic efficiency for discriminating HCC from other forms of liver disease. It is now feasible to further validate this novel plasma‐based biomarker in the large cohort we assembled. What's new? The serological differentiation of hepatocellular carcinoma (HCC) from other liver diseases is challenging and relies mainly on the determination of alpha‐fetoprotein levels. Here, the authors report that human carboxylesterase 1 (hCE1), a liver‐specific serine esterase, is more potent and specific than alpha‐fetoprotein in distinguishing cancer from other liver diseases, in particular cirrhosis. The combination of hCE1 and alpha‐fetoprotein shows synergistic potential for greater specificity and sensitivity in early diagnosis and may be used in the future as a potential diagnostic and surveillance tool to monitor patients with liver cirrhosis for HCC development.