Evaluation of circulating activin-A as a serum marker of hepatocellular carcinoma

Because in experimental hepatocarcinogenesis apoptosis increases from norma l to preneoplastic to carcinoma tissue, proapoptotic factors, such as activ in-A, may represent useful markers for hepatocellular carcinoma (HCC). In t his study. serum activin-A was measured in 99 cirrhotic patients, of whom 5 5 had HCC. Activin-A concentrations were higher in HCC patients (median, 2. 33 ng/ml; range, 0.41-8.12) than in patients with nonmalignant cirrhosis (1 .28 ng/ml; range, 0.35-6.25) (P < .05). All 12 patients with activin-A grea ter than 3 ng/ml and serum alpha-fetoprotein greater than 30 ng/ml had HCC, in comparison to 32 of 41 patients who had only one and to Il of 46 patien ts who had both markers below these cutoffs (P < .0001). No correlation was found between activin-A and alpha-fetoprotein in the two groups, whereas i n patients with HCC, activin-A was strictly correlated with serum aspartate aminotransferase (P < .001). Activin-A mRNA for inhibin beta(A) subunit wa s expressed both in tumor and nontumor liver tissues in a case of HCC super imposed on cirrhosis and was not expressed in a case of HCC without cirrhos is. In conclusion, cirrhotic patients with HCC have high serum activin-A. t o the production of which both the cirrhotic liver and the liver tumor are likely to contribute.