J Cancer 2017; 8(8):1347-1354. doi:10.7150/jca.18450

Research Paper

Ratio of Autoantibodies of Tumor Suppressor AIMP2 and Its Oncogenic Variant Is Associated with Clinical Outcome in Lung Cancer

Ji Ye Jung1, Eun Young Kim1, Arum Kim2, Joon Chang1, Nam Hoon Kwon3, Youngji Moon3, Eun Joo Kang3, Jun Sik Sung3, Hyunbo Shim4, Sunghoon Kim3, 5, Yoon Soo Chang2✉

1. Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea;
2. Division of Pulmonology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea;
3. Medicinal Bioconvergence Research Center, Seoul National University, Seoul, Korea;
4. Department of Life Science and Pharmaceutical Science, Ewha Womans University, Seoul, Korea;
5. WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Suwon, Korea.

Abstract

Aminoacyl-tRNA synthetase-interacting multi-functional protein 2 (AIMP2) works as potent tumor suppressor, while its splicing variant lacking exon 2 (AIMP2-DX2) competes with AIMP2 for binding to target proteins and compromises its anti-tumor activity. Assuming that AIMP2 and its variant AIMP2-DX2 could be released out to human sera in pathological condition, we investigated the diagnostic and prognostic usefulness of autoantibodies against AIMP2 and AIMP2-DX2 by measuring their serum levels in 80 normal and lung cancer samples that were matched in age, gender and smoking status. The area under the curve of AIMP2-DX2, AIMP2, and AIMP2-DX2/AIMP2 autoantibody ratio was low (0.416, 0.579, and 0.357, respectively), suggesting limited diagnostic value. A total of 165 lung cancer patients were classified into low and high AIMP2-DX2, AIMP2, and AIMP2-DX2/AIMP2 based on the median expression of each parameter. The high AIMP2-DX2 group was older and had larger tumors (>3 cm) than the low AIMP2-DX2 group. The high AIMP2-DX2/AIMP2 group had higher CYFRA-21 levels and significantly shorter overall survival than the low AIMP2-DX2/AIMP2 group (18.6 vs. 48.9 months, P = 0.021, Log Rank Test). Taken together, autoantibodies against AIMP2-DX2 and AIMP2 are detectable in the human blood and the increased ratio of AIMP2-DX2/AIMP2 is related to poor clinical outcome of lung cancer.

Keywords: Aminoacyl t-RNA synthetase (ARS), Aminoacyl t-RNA synthetase-interacting multi-functional protein 2 (AIMP2), Aminoacyl t-RNA synthetase-interacting multi-functional protein 2-exon 2 deletion (AIMP2-DX2), Autoantibody, Lung cancer.

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How to cite this article:
Jung JY, Kim EY, Kim A, Chang J, Kwon NH, Moon Y, Kang EJ, Sung JS, Shim H, Kim S, Chang YS. Ratio of Autoantibodies of Tumor Suppressor AIMP2 and Its Oncogenic Variant Is Associated with Clinical Outcome in Lung Cancer. J Cancer 2017; 8(8):1347-1354. doi:10.7150/jca.18450. Available from http://www.jcancer.org/v08p1347.htm