Many studies demonstrated that the immune system can recognize the antigenic changes in cancer cells, and further develop autoantibodies against these antigens which have been called tumor-associated antigens (TAAs). During transition from chronic liver disease to hepatocellular carcinoma (HCC), autoantibodies can appear which are not detected in the pre-malignant conditions. In order to explore the possibility and usefulness of using a mini-array of multiple TAAs as an approach in the diagnosis of HCC, a total of 14 TAAs, including IMP1, IMP2/p62, IMP3/Koc, p53, Survivin, p16, CAPERα, CIP2A/p90, RalA, NPM1, MDM2 and 14-3-3 ζ, c-Myc and CyclinB1, were selected for expression of full-length recombinant proteins. Antibodies against 14 TAAs in 30 sera from patients with chronic hepatitis, 30 sera from patients with liver cirrhosis and 76 sera from patients with HCC as well as sera from 16 HCC patients with serial bleeding samples were detected by enzyme-linked immunosorbent assay (ELISA). Positive results were also confirmed by Western blotting. 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. According to the evaluation indexes for accuracy of screening test, the sensitivity and specificity in using a panel of 14 TAAs for immunodiagnosis of HCC was 69.7% and 83.0%, respectively. The interesting finding was that these anti-TAA autoantibodies could be detected at least one year before the diagnosis of HCC, suggesting that using a penal of 14 TAAs for enhancing autoantibody detection would be a valuable approach in the early diagnosis of HCC. The mini-array of 14 TAAs can identify 43.8% HCC patients who shows serum alpha-fetoprotein (AFP) negative. This study deals with the concept of “cancer immunomics” which allows a global analysis of the auto-antibodies against antigens in a neoplasm. It also determinates that malignant transition to HCC is associated with increased autoantibody responses to certain cellular proteins. In summary, the data from this study further support the hypothesis that a customized TAA array can constitute promising and powerful tool for enhancing the serological anti-TAA antibody detection of HCC, especially in patients with serum AFP negative.

Citation Format: Liping Dai, Mei Liu, Qing Zhu, Xinxin Liu, Yurong Chai, Pengfei Ren, Kaijuan Wang, Chunhua Song, Peng Wang, Mingan Wang, Eng M. Tan, Jianying Zhang. Using immunomic approach to enhance tumor-associated autoantibody detection in diagnosis of hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 885. doi:10.1158/1538-7445.AM2014-885