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

Abstract

SUMMARYFas (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 antihepatitis 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 ¼ 0·0015). An arbitrary cut-off level of 3·03 ng/ml (mean þ 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 transmembranedeleted sFas and some contained another sFas lacking the Fas C-terminal. The positive frequency of either sFas (59·0%) or a-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 ¼ 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.

Serum levels of soluble Fas, nitric oxide and cytokines in acute decompensated cirrhotic patients

“…High levels of sFas have also been described in certain chronic liver diseases [20,21] . However, the effects on acute decompensation of chronic liver diseases are not yet known.…”

Soluble Fas in malignant pleural effusion and its expression in lung cancer cells

“…Recent studies have also reported that serum sFas levels of patients with various malignancies including solid tumors 18,19) and hematopoietic malignancies 20,21) were elevated. Furthermore, a correlation of the serum sFas level with the prognosis of patients was observed in several studies.…”

Prognostic Significance of Serum Soluble Fas Level and Its Change during Regression and Progression of Advanced Prostate Cancer

“…sFas binds to and neutralizes Fas ligand, thereby functionally antagonizing the Fas-Fas ligand pathway [6]. Recently serum sFas has been reported to be elevated in patients with malignant diseases including prostate cancer [7][8][9][10][11][12][13]. Patients diagnosed with prostate cancer have also been shown to have significantly higher levels of serum sFas than those with benign prostate hyperplasia [13].…”