TY - JOUR
T1 - Autoantibodies to tumor-associated antigens combined with abnormal alpha-fetoprotein enhance immunodiagnosis of hepatocellular carcinoma
AU - Chen, Yao
AU - Zhou, Yusen
AU - Qiu, Suimin
AU - Wang, Kaijuan
AU - Liu, Siwei
AU - Peng, Xuan Xian
AU - Li, Junfeng
AU - Tan, Eng M.
AU - Zhang, Jian Ying
N1 - Funding Information:
We thank Drs. Thomas M. Wertin and Daniel Kim at William Beaumont Army Medical Center, El Paso, Texas, for providing serum samples which were used for cDNA library screening in this study as well as Ms. Roxanne Megliorino at University of Texas at El Paso for assistance with some of the molecular techniques in this study. This work was supported by National Institutes of Health (NIH) Grants #2S06GM008012, 5G12RR08124, and CA56956, and China 863 Program #2006AA02A40, and China NSF Grant #30872962.
PY - 2010/3/1
Y1 - 2010/3/1
N2 - 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.
AB - 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.
KW - Alpha-fetoprotein (AFP)
KW - Autoantibodies
KW - Hepatocellular carcinoma
KW - Immunodiagnostic markers
KW - Tumor-associated antigens (TAAs)
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U2 - 10.1016/j.canlet.2009.07.016
DO - 10.1016/j.canlet.2009.07.016
M3 - Article
C2 - 19683863
AN - SCOPUS:75949088039
SN - 0304-3835
VL - 289
SP - 32
EP - 39
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -