Abstract 4659: Detection of autoantibodies against tumor-associated antigens (TAAs) improving immunodiagnosis in human osteosarcoma by serological proteome analysis

Abstract

Osteosarcoma (OS) is the most common malignant primary solid bone-tumor. Despite its relatively low incidence rate among overall cancers, it remains one of the most harmful primary malignant tumors in childhood and adolescence. Thus, a critical need in the diagnosis and management of OS is to determine an optimal combination of clinical biomarkers that could detect tumors early with high specificity/sensitivity and with limited invasiveness. The objective of this study is to identify and characterize the targeted tumor-associated antigens (TAAs) as biomarkers in OS by serological proteome analysis (SERPA) approach, and further to analyze the frequency and specificity of anti-TAA antibodies in OS patients. In this initial study, autoantibodies to 29 TAAs were detected by ELISA and Western blotting in 90 sera from patients with OS, Osteochondroma (OC), and age matched normal individuals. Only 8 protein antigens including DSF70, HMGB1, HCC1, RalA, c-myc, AnnexinA1, IMP1, PBP, can induce significantly higher antibody responses in OS patients compared to normal individuals, achieving the highest sensitivity and specificity, 66% and 95%, respectively. The cumulative positive rate of autoantibodies against these eight selected TAAs in OS reached 70.7% with an observed AUC of 0.972 (95% CI: 0.867-0.988), significantly higher than that in normal control sera. Positive results were also confirmed by Western blotting. These preliminary data extensively evidence that not all proteins identified in cancer can be used as TAA biomarkers in OS, and only some of these proteins can induce immune responses, which could be potential TAAs in OS immunodiagnosis or prognosis, and further studies of novel targeted proteins in OS are currently in progress by SERPA approach. In addition, it supports the hypothesis that a customized TAA array can be used for enhancing anti-TAA antibodies detection, and it may constitute a promising and powerful tool for immunodiagnosis of OS. Citation Format: Jitian Li, Manyu Huang, Manli Luo, Liping Dai, Wen Xie, Xiaofei Qin, Zongchang Han, Wuyin Li, Jianying Zhang. Detection of autoantibodies against tumor-associated antigens (TAAs) improving immunodiagnosis in human osteosarcoma by serological proteome analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4659. doi:10.1158/1538-7445.AM2017-4659