Abstract
// Li-Ping Dai 1,2,3,* , Ji-Tian Li 3,* , Xiao Wang 1,2,3 and Jian-Ying Zhang 1,2,3 1 Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China 2 Henan Key Laboratory for Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China 3 Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, USA * Li-Ping Dai and Ji-Tian Li contributed equally to this work Correspondence to: Jian-Ying Zhang, email: jzhang@utep.edu Li-Ping Dai, email: lpdai@zzu.edu.cn Keywords : hepatocellular carcinoma (HCC); autoantibody; MDM2; p53 Received: July 13, 2017 Accepted: October 30, 2017 Epub: January 03, 2018 Abstract Purpose: The human homologue of the mouse double minute 2 (MDM2) is a transcriptional target and negative regulator of p53. This study aims to investigate the immune response of MDM2 and p53 in hepatocellular carcinoma (HCC). Methods: The autoantibodies were examined by immunoassay in individual sera from 160 HCC patients and 89 normal controls, as well as 76 sequential serum samples from an independent group of 16 HCC patients. The receiver operating characteristic (ROC) analysis was conducted for autoantibody for the distinguishing of HCC from controls. Results: Anti-MDM2 and anti-p53 autoantibodies could distinguish HCC patients from normal individuals in derivation set with area under curve (AUC) of 0.752 and 0.844, as well as in validation set with AUC of 0.658 and 0.703, respectively. The frequencies of anti-MDM2 (30.3%) and anti-p53 (32.9%) autoantibodies were significantly higher in HCC patients than that in normal individuals (10.1%). When anti-MDM2 and anti-p53 autoantibodies combined together, the positive frequency in HCC patients increased to 44.7% which was still significantly higher than that in normal individuals (18.0%). By using longitudinal preclinical samples, 62.5% of patients were observed with anti-MDM2 or anti-p53 autoantibody positive one year prior to diagnosis of HCC. Serum level of autoantibodies against these two TAAs were positively associated with each other ( r = 0.500, P < 0.001). Conclusions: MDM2 and p53 are autoantigens that elicit autoimmune responses in HCC and can be the potential biomarkers for the early detection or predictor of HCC.
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