Jung Ji Ye, Kim Eun Young, Kim Arum, Chang Joon, Kwon Nam Hoon, Moon Youngji, Kang Eun Joo, Sung Jun Sik, Shim Hyunbo, Kim Sunghoon, Chang Yoon Soo
Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Division of Pulmonology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
J Cancer. 2017 May 12;8(8):1347-1354. doi: 10.7150/jca.18450. eCollection 2017.
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, = 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.
氨酰-tRNA合成酶相互作用多功能蛋白2（AIMP2）作为一种有效的肿瘤抑制因子发挥作用，而其缺少外显子2的剪接变体（AIMP2-DX2）与AIMP2竞争结合靶蛋白，从而损害其抗肿瘤活性。假设在病理状态下AIMP2及其变体AIMP2-DX2可释放到人体血清中，我们通过测量80例年龄、性别和吸烟状况相匹配的正常人和肺癌患者样本中的血清水平，研究了抗AIMP2和AIMP2-DX2自身抗体的诊断和预后价值。AIMP2-DX2、AIMP2和AIMP2-DX2/AIMP2自身抗体比值的曲线下面积较低（分别为0.416、0.579和0.357），表明诊断价值有限。根据每个参数的中位数表达，将165例肺癌患者分为AIMP2-DX2、AIMP2和AIMP2-DX2/AIMP2低表达组和高表达组。高AIMP2-DX2组患者年龄较大，肿瘤较大（>3 cm），高于低AIMP2-DX2组。高AIMP2-DX2/AIMP2组CYFRA-21水平较高，总生存期明显短于低AIMP2-DX2/AIMP2组（18.6个月对48.9个月，P = 0.021，对数秩检验）。综上所述，人体血液中可检测到抗AIMP2-DX2和AIMP2的自身抗体，AIMP2-DX2/AIMP2比值升高与肺癌患者的不良临床结局相关。
