Investigation of new autoantibodies in urothelial bladder cancer for biomarker discovery using immunoproteomics.

Abstract

Background: Tumor-associated antigens (TAAs) lead to the production of tumor-specific autoantibodies (anti-TAA autoantibodies) by triggering the humoral immune system which can be used as candidate biomarkers. This study aims to investigate TAAs proteins eliciting humoral responses in different stages of urothelial bladder carcinoma (UBC) using an immunoproteomics approach to find novel biomarkers for the clinical management of the disease.

Methods: Total proteins were obtained from the newly established UBC cell line, JAM-ICR, and separated by two-dimensional gel electrophoresis (2DE). These proteins were then immobilized using pooled serum samples from healthy individuals, autoimmune and UBC patients at different stages. The immunoreactive spots in UBC patient samples were identified by mass spectrometry and verified with several databases such as GEPIA and Enrichr databases.

Results: Through the comparison of the immunoreactivity pattern of serums, we were able to identify eight specific proteins using LC-MS. Patients with muscle invasion showed increased expression of ENO1, VDAC2, AKR1B1, SDF2L1, PRDX6, PSME1, HSPB1 and PHB1 compared to controls. In addition, non-muscle invasive patients showed overexpression of ENO1, VDAC2, AKR1B1, and PRDX6 compared to controls. In addition to their diagnostic function, PRDX6, ENO1, VDAC2, and PHB1 have been demonstrated to possess prognostic capabilities in patients with UBC. Interestingly, these proteins were mainly associated with cellular growth and anti-apoptotic activity.

Conclusion: In this study, eight anti-TAA autoantibodies were identified that have the potential to serve as diagnostic and prognostic biomarkers. These could represent a valuable panel of biomarkers for the management of UBC.