Elevated serum levels of soluble Fas/APO‐1 (CD95) in patients with hepatocellular carcinoma

• Published in: Clinical and experimental immunology Vol. 112; no. 2; pp. 166 - 171
• Main Authors: JODO, S, KOBAYASHI, S, NAKAJIMA, Y, MATSUNAGA, T, NAKAYAMA, N, OGURA, N, KAYAGAKI, N, OKUMURA, K, KOIKE, T
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01-05-1998; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - immunology; Enzyme-Linked Immunosorbent Assay; fas Receptor - blood; Female; hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; Host-tumor relations. Immunology. Biological markers; Humans; liver cirrhosis; Liver Cirrhosis - blood; Liver Cirrhosis - immunology; Liver Neoplasms - blood; Liver Neoplasms - immunology; Male; Medical sciences; Middle Aged; Original; Solubility; soluble Fas; Tumor Escape - immunology; Tumors; Human; Hepatitis B surface antigen; Biological marker; Hepatic disease; Hepatocellular carcinoma; Malignant tumor; Soluble form; Cell surface; Virus; Antigen; Cirrhosis; Digestive diseases; Serum; Flaviviridae; Hepatitis C virus; Hepacivirus
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1998.00569.x

Fas (APO‐1/CD95)‐mediated apoptosis plays an important role in liver cell destruction in viral hepatitis. Using sandwich ELISA, we measured serum levels of soluble Fas (sFas) in patients with hepatocellular carcinoma (HCC) who were positive for hepatitis B surface antigen (HBsAg) or anti‐hepatitis C virus (HCV) antibody. sFas levels were significantly higher in HCC patients (median 4.07 ng/ml; range 0.14–29.18 ng/ml) than levels in age‐matched healthy donors (0.29 ng/ml; 0–4.90 ng/ml) (P < 0.0001) and HBsAg or anti‐HCV antibody‐positive patients with liver cirrhosis (LC) (2.16 ng/ml; 0.24–8.39 ng/ml) (P = 0.0015). An arbitrary cut‐off level of 3.03 ng/ml (mean + 3 s.d. of controls) revealed the positive frequency of sFas in each group: 1.7% in healthy subjects, 25.9% in LC, and 59.0% in HCC (sensitivity 59.0% and specificity 74.1%). All HCC sera tested contained transmembrane‐deleted sFas and some contained another sFas lacking the Fas C‐terminal. The positive frequency of either sFas (59.0%) or α‐fetoprotein (AFP) (57.4%) in HCC patients reached 77.0%. HCC patients with multiple tumour foci (7.53 ng/ml; 1.40–29.18 ng/ml) had significantly higher sFas levels than did patients with a solitary tumour (2.70 ng/ml; 0.14–19.0 ng/ml) (P = 0.003). In all of the sFas‐positive patients with a solitary tumour, surgical removal of the tumour reduced sFas levels to the negative in the first post‐op week. These findings suggest that sFas may be closely linked with HCC and may be a candidate for a clinical parameter for HCC.