Abstract 454: Identification and characterization of tumor-associated antigens (TAAs) and anti-TAAs autoantibodies as biomarkers in immunodiagnosis of human osteosarcoma by serological proteome analysis

Abstract

Osteosarcoma (OS) is the most common highly 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. Although some tumor markers like mutant p53 can be potentially used as biomarker to detect OS, the sensitivity and specificity are not optimal, especially for early diagnosis. The establishment of a methodology to identify patient with early stage of OS remains to be investigated. There has been a growing interest in using serum autoantibodies against tumor-associated antigens (TAAs) as serological cancer biomarkers, which stems from the notion that anti-TAA antibodies are “sensors” or “reporters” of molecular events associated with tumorigenesis. The objective of this study is to identify and characterize the targeted TAAs as biomarkers in OS, and further to analyze the frequency and specificity of autoantibodies in OS patients. In this initial study, we have tested 35 sera from OS patients, 12 sera from Osteochondroma (OC) patients and 32 age-matched normal human sera (NHS), for the presence of autoantibodies to the TAAs from extracted protein antigens from U2-OS culture cells in 1-D Western blot and by indirect immunofluorescence (IIF). Autoantibodies were detected in 34 of 35 (97.1%) sera from patients with OS, which were significantly higher than that in NHS (12.5%, 4/32). In contrast, there is no significate association between OC and NHS group, which implies that the OS sera may encompass more specific autoantibodies than OC sera. Interestingly, 35% (7/20), 25% (5/20), 20% (4/20) and 35% (7/20) OS sera were identified by 1D Western blotting analysis containing antibodies against unknown cellular protein antigens around 35 kD, 45 kD, 55 kD and 60 kD respectively. Additionally, no reactivity with the 45 kD and 55 kD protein was detected in 32 NHS. In the further study, these cellular proteins targeted by serum antibodies in OS will be identified by using serological proteome analysis (SERPA) approach. This preliminary data supports that autoimmune responses to certain cellular proteins maybe a by-product in the transformation to OS, and further studies of novel targeted proteins in OS may provide insights into how these proteins might be involved in malignancy. Key Words: Osteosarcoma (OS), Tumor-associated antigens (TAAs), Serological proteome analysis (SERPA), Cancer early detection, Immunodiagnosis Citation Format: Jitian Li, Manyu Huang, Manli Luo, Pei Li, Wen Xie, Zongchang Han, Wuyin Li, Jianying Zhang. Identification and characterization of tumor-associated antigens (TAAs) and anti-TAAs autoantibodies as biomarkers in immunodiagnosis of human osteosarcoma by serological proteome analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 454.