Autoantibodie against intracellular antigens are commonly found in a number of systemic autoimmune diseases. Their utility in providing insights into molecular and cellular biology and in the differential diagnosis of autoimmune diseases is well documented. Autoimmune phenomena manifested as antibodies to cellular components have been described in many types of cancer. Liver cancer, especially hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Although HCC is not a common type of cancer in the United States, HCC affects the Hispanic population at a rate double that of the White population in this country. Texas has the second largest Hispanic population, representing 32.0% of its citizens. The objective of this study is to analyze the frequency and specificity of autoantibodies in HCC patients from Texas, and further to identify and characterize the targeted tumor-associated antigens. In this study, 152 sera from HCC patients, 64 sera from patients with chronic liver diseases, and 30 sera from normal human individuals were examined for autoantibodies using immunofluorescence assay and Western blotting. Autoantibodies were detected in 113 of 152 (74.3%) HCC sera, which was significantly higher than that in normal human sera. Of the interest is that of 152 HCC sera, 26 (17.1%) sera were identified by Western blotting analysis containing antibodies against an unknown 45kDa cellular protein. No reactivity with the 45 kDa protein was detected in 64 chronic liver disease sera, and 30 normal human sera. Subcellular fractionation of HepG2 (hepatocellular carcinoma) cells showed the 45 kDa proteins were predominantly in the cytoplasm, and were not found in the nuclear fraction. The analysis using immunohistochemistry on HepG2 cells confirmed that the sera with antibodies to the 45 kDa antigen appeared to have the cytoplasmic staining patterns. Further identification of this cellular protein using two-dimensional gel electrophoresis (2DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed that six proteins around 45kDa were identified, including heterogeneous nuclear ribonucleo protein F (46kDa), beta-actin-like protein 2 (42 kDa), KRT18 Keratin (48kDa), isocitrate dehydrogenase (47kDa), TUFM Tu translation elongation factor (50 kDa), and 3-ketoacyl-CoA thiolase (42.5 kDa). This preliminary data supports that autoimmune responses to certain cellular proteins may be a by-product in the transformation to HCC, and further studies of novel targeted autoantigens in Hispanic HCC may provide insights into how these proteins might be involved in malignancy.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1581.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009