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Sci Rep. 2019 Jul 30;9(1):11059. doi: 10.1038/s41598-019-47365-4.

Serum anti-EIF3A autoantibody as a potential diagnostic marker for hepatocellular carcinoma.

Heo CK1,2, Hwang HM1,2, Lee HJ3,4, Kwak SS1,5, Yoo JS6, Yu DY7, Lim KJ3, Lee S8, Cho EW9,10.

Author information

1
Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, South Korea.
2
College of Bioscience and Biotechnology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, South Korea.
3
Proteometech Inc., 1101 Wooree Venture Town, 466 Gangseo-ro, Gangseo-gu, Seoul, 03722, South Korea.
4
Graduate Program for Nanomedical Science, Yonsei University, 50 Yonsei-ro Seodaemun-gu, Seoul, 03722, South Korea.
5
Department of Functional Genomics, University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, South Korea.
6
Biomedical Omics Group, Korea Basic Science Institute, 162 YeonGuDanji-Ro, Ochang-eup, Cheongju, Chungbuk, 28119, South Korea.
7
Disease Model Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, South Korea.
8
College of Bioscience and Biotechnology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, South Korea. leesoojin@cnu.ac.kr.
9
Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, South Korea. ewcho@kribb.re.kr.
10
Department of Functional Genomics, University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, South Korea. ewcho@kribb.re.kr.

Abstract

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.

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