title: Autoantibodies to tumor-associated antigens combined with abnormal alpha-fetoprotein enhance immunodiagnosis of hepatocellular carcinoma.
abstract: The identification and characterization of tumor-associated antigens (TAAs) and their use in antigen mini-arrays for cancer immunodiagnosis has been of interest recently as an approach to cancer detection. In this study, autoantibodies in sera from a patient with HCC were used as probes to immunoscreen a HepG2 cDNA expression library for the identification of TAAs involved in malignant liver transformation. Recombinant proteins from two genes identified in this manner, Sui1 and RalA were expressed, purified and used as antigens in immunoassays to detect the presence of antibodies in sera from 77 patients with HCC, 30 with chronic hepatitis (CH), 30 with liver cirrhosis (LC) and 82 normal human sera (NHS). The prevalence of antibody to Sui1 and RalA in HCC were 11.7% (9/77) and 19.5% (15/77), respectively, which were significantly higher than prevalence in liver cirrhosis (3.3% and 3.3%), chronic hepatitis (0% and 0%) and normal human sera (0% and 0%). When Sui1 and RalA were added to a panel of eight other TAAs used in a previous study, the final cumulative prevalence of anti-TAA antibodies in HCC to the 10 TAA array was raised to 66.2% (51/77). The specificity for HCC compared with LC, CH and NHS, was 66.7%, 80.0%, and 87.8%, respectively. When anti-TAA was added to abnormal serum AFP as combined diagnostic markers, it raised the diagnostic sensitivity from 66.2% to 88.7%. AFP and anti-TAA were independent markers and the simultaneous use of these two markers significantly resulted in the increased sensitivity of HCC detection.
authors.affiliation: Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
authors.forename: Suimin
authors.initials: S
authors.lastname: Qiu
authors.forename: Kaijuan
authors.initials: K
authors.lastname: Wang
authors.forename: Siwei
authors.initials: S
authors.lastname: Liu
authors.forename: Xuan-Xian
authors.initials: XX
authors.lastname: Peng
authors.forename: Junfeng
authors.initials: J
authors.lastname: Li
authors.forename: Eng M
authors.initials: EM
authors.lastname: Tan
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000276:immunology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007159:Immunologic Tests; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012015:Reference Standards; D012680:Sensitivity and Specificity; D015854:Up-Regulation; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis; D020725:ral GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D018076:DNA, Complementary; C410108:EIF1 protein, human; D039642:Eukaryotic Initiation Factors; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; C492198:RALA protein, human; D020725:ral GTP-Binding Proteins
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