An Exploratory Proteomic Study Delineating The Local And Systemic Immune-Oncologic Profile Of Urinary Bladder Cancer Patients

Introduction Cancer of the urinary bladder (UBC) primarily derives from the urothelium, encompassing the inner surface of the bladder. Tumors infiltrating the detrusor muscle are categorized as muscle-invasive bladder cancer (MIBC) and constitutes 20-25% of all newly diagnosed UBC. These tumors are more likely to spread to peripheral organs and lymph nodes, compared to the more prevalent (75-80%) non-muscle invasive bladder cancer subtype (NMIBC). To this end, cystoscopy and urine cytology are the current standards for diagnosing and surveying UBC, which provides limited information regarding their immunological profile. Methods We performed a targeted human protein biomarker analysis from collected plasma and urine from a well-categorized UBC patient cohort. In short, 92 immuno-oncology related proteins were investigated by a novel Proximity Extension Assay multiplex technology (Olink). Results The assayed proteins depicted a heterogenic immune profile. Neither PCA or unsupervised hierarchical clustering identified distinct groups associated with clinical features. However, a direct comparison between non-invasive and invasive cases resulted in 4 differentially expressed proteins (p Conclusions This study highlights the heterogenic nature of the immunogenic landscape in UBC and its potential role in immunotherapy treatment responses. Our findings indicate that systemic MMP levels should be further explored as a potential liquid biopsy marker for patient stratification purposes. The role of MMPs in UBC may be linked to an invasive tumor characteristic, as shown by previous UBC studies where high levels of MMPs correlated to reduced overall survival.