Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens.

BACKGROUND: Multiple antigen miniarrays used for detecting autoantibodies to tumor-associated antigens (TAAs) can be a useful approach for cancer detection and diagnosis. We here address a very specific question: might there be autoimmune responses to TAAs which precede clinical detection of hepatocellular carcinoma (HCC) in HBV and HCV chronic liver disease patients under continuous medical surveillance, and if so, could these anti-TAAs be added to the armamentarium of diagnostic tests? METHODS: We here examine the utility of a panel of 12 TAAs for the diagnosis of hepatocellular carcinoma (HCC). We derived a predictive rule for the presence of HCC based on the panel, from a cohort comprising 160 HCC patients and 90 normals. We then applied this rule to sequential anti-TAA data from a cohort of 17 HCC patients, from whom this information was available prior to diagnosis. RESULTS: The predictors (autoantibodies to HCC1, P16, P53, P90, and survivin) indicated the presence of HCC prior to diagnosis in 16 of the 17 patients, at a median lead time of 0.75 year. CONCLUSIONS: We believe these findings warrant further study of anti-TAA profiles as biomarkers for primary or early diagnosis of HCC.

Using immunomic approach to enhance tumor-associated autoantibody detection in diagnosis of hepatocellular carcinoma.

To explore the possibility of using a mini-array of multiple tumor-associated antigens (TAAs) as an approach to the diagnosis of hepatocellular carcinoma (HCC), 14 TAAs were selected to examine autoantibodies in sera from patients with chronic hepatitis, liver cirrhosis and HCC by immunoassays. Antibody frequency to any individual TAA in HCC varied from 6.6% to 21.1%. With the successive addition of TAAs to the panel of TAAs, there was a stepwise increase of positive antibody reactions. The sensitivity and specificity of 14 TAAs for immunodiagnosis of HCC was 69.7% and 83.0%, respectively. This TAA mini-array also identified 43.8% of HCC patients who had normal alpha-fetoprotein (AFP) levels in serum. In summary, this study further supports the hypothesis that a customized TAA array used for detecting anti-TAA autoantibodies can constitute a promising and powerful tool for immunodiagnosis of HCC and may be especially useful in patients with normal AFP levels.