Abstract 2585: Immunoseroproteomic profiling in autoantibodies to ENO1 as potential biomarkers in immunodiagnosis of osteosarcoma by serological proteome analysis (SERPA) approach

Abstract

Background: 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. It is now evident that serum autoantibodies against tumor-associated antigens (TAAs) could be used as serological cancer biomarkers in types of cancers. Methods: Serological proteome analysis (SERPA) approach was applied to profile anti-TAA autoantibody responses in sera from patients with OS, and Normal Human, and explore differences of these responses. This approach can detect autoantibodies to TAAs that could serve as clinical biomarkers and immunotherapeutic agents. Sera from OS, Osteochondroma (OC) and Normal Human Sera (NHS) were probed by immunoblotting against cellular proteins extracted from U2-OS and Saos-2 cell lines, with OS sera showing stronger immunoreactivity. MALDI-TOF/TOF Mass Spectrometry (MS) analysis of immunoreactive protein spots revealed that several OS sera contained autoantibodies to a number of proteins, particularly to alpha-enolase (ENO1). Results: Analysis of 172 serum samples from patients with OS, OC and NHS by ELISA showed higher frequency of anti-ENO1 autoantibodies in OS sera compared to others. Interestingly, descant of ENO1 immunoreactivity was observed in most patients after treatments, which may imply a potential association between anti-ENO1 autoantibody titers and disease progression. Nine of twelve sera reacted strongly against purified ENO1, but 3 weakly against purified ENO1, which indicates 75.0% sera with positive optimal density values from ELISA were consistently positive in Western blotting. The expression of ENO1 in Osteosarcoma tissues was evaluated by immunohistochemistry in tumor microarray. Conclusion: Our intriguing findings firstly demonstrate that ENO1 is one of autoantigens that elicit autoimmune responses in OS and can be used as biomarkers in immunodiagnosis and progression of OS. Key words: Osteosarcoma (OS), Tumor-associated antigen (TAA), Serological proteome analysis (SERPA), ENO1, Immunodiagnosis. Citation Format: Jitian Li, Manyu Huang, Liping Dai, Zongchang Han, Xiaofei Qin, Wen Xie, Wei Qian, Wuyin Li, Jianying Zhang. Immunoseroproteomic profiling in autoantibodies to ENO1 as potential biomarkers in immunodiagnosis of osteosarcoma by serological proteome analysis (SERPA) approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2585.