Identification of tumor-associated antigens in human hepatocellular carcinoma by autoantibodies

Abstract

Hepatocellular carcinoma (HCC) is a major cause of death in Asian countries. The false-negative rate with serum alpha-fetaprotein level alone can reach 40% for early stage HCC patients. Due to the lack of sensitive and specific tumor markers for early diagnosis, it is impossible for HCC patients to receive effective therapy. However, tumor antigens can be recognized by immune cells and be rejected in immune responses. In order to identify antigens which may be used as new markers and immunotherapy targets for HCC, a cDNA expression library derived from an HCC sample was constructed, which was screened with mixed autologous and allogenic serum of HCC patients. Seventeen different HCC antigens were obtained, which are classified as tumor-associated antigens. A panel of allogenic sera from patients with chronic hepatitis, liver cirrhosis, HCC and other tumor entities and sera from health volunteers, was used for frequency analysis of antibody responses. Four of 17 antigens, including eukaryotic translation initiation factor 3, subunit I, lactate dehydrogenase 1, A chain, replication factor C2, 40 kDa and mitochondrial carrier triple repeat 1, reacted predominantly with sera from patients with HCC (31.8, 45.5, 27.3 and 50.0% respectively). Patients (81.8%) with HCC had the antibody against at least one of these four antigens, which indicates that disease-specific humoral response against these antigens was induced in HCC patients and the corresponding antibodies may be used as tumor markers for HCC.