De‐novo humoral immune responses to cancer‐associated autoantigens during transition from chronic liver disease to hepatocellular carcinoma

• Published in: Clinical and experimental immunology Vol. 125; no. 1; pp. 3 - 9
• Main Authors: Zhang, J. Y., Zhu, W., Imai, H., Kiyosawa, K., Chan, E. K. L., Tan, E. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.2001; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Antigens, Neoplasm - immunology; Autoantibodies - immunology; Autoantigens - immunology; Biological and medical sciences; cancer antigens; cancer autoimmunity; Cancer Immunology; Carcinoma, Hepatocellular - etiology; Carcinoma, Hepatocellular - immunology; CENP‐F; Chromosomal Proteins, Non-Histone - immunology; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - immunology; Hepatitis, Autoimmune - complications; Hepatitis, Autoimmune - immunology; hepatocellular carcinoma; Humans; insulin-like growth factor II; Liver Cirrhosis - complications; Liver Cirrhosis - immunology; Liver Neoplasms - etiology; Liver Neoplasms - immunology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Microfilament Proteins; Middle Aged; p62; RNA-Binding Proteins - immunology; Tumors; Autoimmunity; Human; Immune response; Liver; Hepatic disease; Hepatocellular carcinoma; Malignant tumor; Carcinogenesis; De novo; Cirrhosis; Chronic; Autoantigen; Malignant transformation; Cell cycle; Digestive diseases; Humoral immunity; Nuclear protein
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2001.01585.x

A feature of hepatocellular carcinoma (HCC) is that antecedent liver cirrhosis and chronic hepatitis are common precursor conditions and during transition to malignancy some patients develop autoantibodies which were not present during the preceding chronic liver disease phase. Serum samples from such patients can be used to immunoscreen cDNA expression libraries to identify genes encoding the new autoantigens. We demonstrate here the de novo appearance of antibodies to p62, a cytoplasmic protein which has been shown to bind to a developmentally regulated fetal species of insulin‐like growth factor II (IGF‐II) mRNA. Another antibody appearing during the transition period was against CENP‐F, a cell cycle‐related nuclear protein with maximum expression in the G2 and M phases of the cell cycle and previously shown to have a high association with malignancy. In three additional patients in whom serial serum samples were examined, new appearance of anti‐p62 was detected in two patients and anti‐CENP‐F in one patient. This study demonstrates that transition to malignancy can be associated with autoantibody responses to certain cellular proteins which might have some role in tumorigenesis.