Immunoseroproteomic profiling in autoantibody to ENO1 as potential biomarker in immunodiagnosis of osteosarcoma by serological proteome analysis (SERPA) approach

Abstract

Osteosarcoma (OS) is the most common highly malignant primary solid bone tumor. Despite its relatively low incidence among 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. Serological proteome analysis (SERPA) approach was applied to profile anti-TAA autoantibody response in sera from patients with OS and normal human, as well as explore difference between this response. This approach can detect autoantibodies that could serve as clinical biomarkers and immunotherapeutic agents. Enzyme-linked immunosorbent assay (ELISA) and Western blotting were further used to validate the level of identified TAAs. ENO1 as a 47kD TAA in OS was identified and characterized by SERPA. Analysis of 172 serum samples with OS, osteochondroma (OC), and normal human sera (NHS) by ELISA showed higher frequency of anti-ENO1 autoantibodies in OS sera compared to others. Interestingly, decrease 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 three reacted weakly against purified ENO1, which indicated 75.0% sera with positive optimal density values from ELISA were consistently positive in Western blotting. The expression of ENO1 in OS tissues was evaluated by immunohistochemistry in tumor microarray. ENO1 was one of the autoantibodies that elicit autoimmune responses in OS and can be used as biomarkers in immunodiagnosis and progression of OS.

A 3D-printed scaffold-based osteosarcoma model allows to investigate tumor phenotypes and pathogenesis in an in vitro bone-mimicking niche

“… Biomarker Increased or decreased Sampled tissue Ref. ENO1 Increased Primary tumor [ 53 ] TGFB1 Increased Primary tumor, serum [ 54 , 55 ] PLOD1 Increased Primary tumor, metastasis [ 56 ] MVP Increased Primary tumor, metastasis [ 57 ] VEGF Increased Primary tumor, metastasis [ [58] , [59] , [60] ] EHD1 Increased Primary tumor [ 61 ] HER2 (ERBB2) Increased Primary tumor [ 62 , 63 ] HES4 Increased Primary tumor [ 64 ] CXCR4 Increased Primary tumor, metastasis [ 58 , 65 ] hCG Increased Primary tumor, serum [ 66 , 67 ] PDGF Increased Primary tumor, metastasis [ 68 ] ASS Decreased Primary tumor, metastasis [ 69 ] CDH11 Decreased Primary tumor, metastasis [ 70 ] ENO1: enolase 1; TGFB1: transforming growth fac...…”

Evaluating a Panel of Autoantibodies Against Tumor-Associated Antigens in Human Osteosarcoma

“…Two osteosarcoma cell lines U2-OS and Saos-2 were cultured. Specific experimental methods and results were based on our published literature ( Li et al, 2021 ).…”

“…Our previous study ( Li et al, 2021 ) has found a panel of eight candidate serum autoantibodies with SERPA. In this study, these eight candidate autoantibodies were detected by indirect ELISA.…”