Proteomic research and diagnosis in bladder cancer: state of the art review

Abstract

Purpose: Proteomic biomarkers have been emerging as alternative methods to the gold standard procedures of cystoscopy and urine cytology in the diagnosis and surveillance of bladder cancer (BC). This review aims to update the state of the art of proteomics research and diagnosis in BC. Materials and Methods: We reviewed the current literature related to BC research on urinary, tissue, blood and cell line proteomics, using the Pubmed database. Findings: Two urinary protein biomarkers are FDA-approved (NMP22® and BTA® tests), only if performed along with cystoscopy for surveillance after initial diagnosis, but not in the primary diagnostic setting due to high false-positive rates in case of infections, stones and hematuria. There are a great number of non-FDA approved proteins being studied, with good preliminary results; panels of proteins seem valuable tools to be refined in ongoing trials. Blood proteins are a bigger challenge, because of the complexity of the serum protein profile and the scarcity of blood proteomic studies in BC. Previous studies with the BC tissue proteome do not correlate well with the urinary proteome, likely due to the tumor heterogeneity. Cell line proteomic research helps in the understanding of basic mechanisms that drive BC development and progression; the main difficulty is culturing low-grade tumors in vitro, which represents the majority of BC tumors in clinical practice. Conclusion: Protein biomarkers have promising value in the diagnosis, surveillance and prognostic of BC. Urine is the most appropriate body fluid for biomarker research in BC due to its easiness of sampling, stability and enrichment of shed and secreted tumor-specific proteins. Panels of biomarkers may exhibit higher sensitivity than single proteins in the diagnosis of BC at larger populations due to clinical and tumor heterogeneity. Prospective clinical trials are warranted to validate the relevance of proteomic data in the clinical management of BC.

Current look at the most promising proteomic and glycomic biomarkers of bladder cancer

“…The importance of glycomic biomarkers, biomarkers based on the detection of altered glycosylation, for early diagnosis, prognosis, and therapy of many diseases, including cancer, is growing rapidly, and this applies to BC as well. In recent years, there were several published reviews dedicated to the glycan and glycoprotein changes related to BC (Jian et al 2020 ; Jin et al 2021 ; López-Cortés et al 2021 ; Wilson et al 2021 ). In this section, we discuss the newest research on BC glycomic biomarkers that were reported during the last 2 years.…”

Exploration of potential biomarkers for early bladder cancer based on urine proteomics

“…Screening methods for bladder cancer include urine exfoliation cytology, cystoscopy and tumor biomarker assessment ( 9 ). Urine cytology has poor sensitivity for low-grade bladder cancer (sensitivity 25.0-48.0%) ( 10 ). Cystoscopy is the gold standard for diagnosing bladder cancer; however, it is an invasive examination that may lead to risks of bleeding, infection, etc., and easily causes patient discomfort ( 11 ).…”

Deciphering Urogenital Cancers through Proteomic Biomarkers: A Systematic Review and Meta-Analysis

“…Furthermore, proteomics facilitates the elucidation of signaling pathways and the identification of therapeutic targets. Several recent studies have demonstrated the potential of proteomics in the identification of biomarkers and therapeutic targets in urogenital cancers, highlighting the importance of conducting further research in clinical settings [ 13 , 14 , 15 ]. While a number of studies on the role of proteomics in urogenital cancers have begun to be published, a comprehensive synthesis and analysis of these findings is lacking.…”