Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, South Korea.
College of Bioscience and Biotechnology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, South Korea.
Sci Rep. 2019 Jul 30;9(1):11059. doi: 10.1038/s41598-019-47365-4.
Tumor-associated autoantibodies are promising diagnostic biomarkers for early detection of tumors. We have screened a novel tumor-associated autoantibody in hepatocellular carcinoma (HCC) model mice. Its target antigen was identified as eukaryotic translation initiation factor 3 subunit A (EIF3A) by proteomic analysis, and the elevated expression of EIF3A in HCC tissues of tumor model mice as well as human patients was shown. Also, its existence in tumor-derived exosomes was revealed, which seem to be the cause of tumor-associated autoantibody production. To use serum anti-EIF3A autoantibody as biomarker, ELISA detecting anti-EIF3A autoantibody in human serum was performed using autoantibody-specific epitope. For the sensitive detection of serum autoantibodies its specific conformational epitopes were screened from the random cyclic peptide library, and a streptavidin antigen displaying anti-EIF3A autoantibody-specific epitope, XC90p2(-CPVRSGFPC-), was used as capture antigen. It distinguished patients with HCC (n = 102) from healthy controls (n = 0285) with a sensitivity of 79.4% and specificity of 83.5% (AUC = 0.87). Also, by simultaneously detecting with other HCC biomarkers, including alpha-fetoprotein, HCC diagnostic sensitivity improved from 79.4% to 85%. Collectively, we suggest that serum anti-EIF3A autoantibody is a useful biomarker for the diagnosis of HCC and the combinational detection of related biomarkers can enhance the accuracy of the cancer diagnosis.
肿瘤相关自身抗体是肿瘤早期检测有前景的诊断生物标志物。我们在肝癌（HCC）模型小鼠中筛选了一种新型肿瘤相关自身抗体。通过蛋白质组学分析鉴定其靶抗原为真核翻译起始因子 3 亚基 A（EIF3A），并显示肿瘤模型小鼠和人类患者 HCC 组织中 EIF3A 的表达升高。此外，还揭示了其在肿瘤衍生的外泌体中的存在，这似乎是产生肿瘤相关自身抗体的原因。为了将血清抗-EIF3A 自身抗体用作生物标志物，使用自身抗体特异性表位通过 ELISA 检测人血清中的抗-EIF3A 自身抗体。为了敏感检测血清自身抗体，从随机环肽文库中筛选其特异性构象表位，并使用抗-EIF3A 自身抗体特异性表位展示的链霉亲和素抗原 XC90p2(-CPVRSGFPC-)作为捕获抗原。它以 79.4%的灵敏度和 83.5%的特异性（AUC=0.87）将 HCC 患者（n=102）与健康对照者（n=0285）区分开来。此外，通过同时检测其他 HCC 标志物，包括甲胎蛋白，HCC 诊断的灵敏度从 79.4%提高到 85%。综上所述，我们认为血清抗-EIF3A 自身抗体是 HCC 诊断的有用生物标志物，相关生物标志物的联合检测可以提高癌症诊断的准确性。
