Glycoprotein biomarkers for bladder cancer detection.

The literature review explores the current findings on the use of glycoproteins and glycans biomarkers present in urine and urinary extracellular vesicles (EVs) as indicators of bladder cancer (BC). We further investigated their effectiveness in differentiating between non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) forms, as well as their application in post-treatment patient monitoring. Cystoscopy remains the diagnostic gold standard; however, it is an invasive procedure that requires hospitalization. In contrast, urine cytology exhibits low sensitivity for detecting low-grade non-muscle-invasive bladder cancer (NMIBC). Tumor-associated alterations in N- and O-glycosylation, sialylation, and fucosylation are biomarkers that can be quantified using various complementary analytical techniques. These include high-resolution glycoproteomic discovery tools such as mass spectrometry, motif-level profiling tools such as lectin-based assays, and scalable clinical quantification tools such as targeted immunoassays. Multiplex urinary glycoprotein panels used in retrospective cohort studies have areas under the curve (AUC) of 0.82-0.96, and have better sensitivity than cytology in low-grade disease. EV-derived N-glycan signatures have shown preliminary NMIBC-MIBC discrimination (validation AUCs 0.86-0.88) but live in the retrospective validation phase. Preanalytical standardization, which entails the selection of specimens, storage, normalization, and harmonized quality control, is a barrier of critical importance in translation. Although the biological rationale and analytical feasibility of this approach are well established, its clinical applicability remains to be demonstrated. Glycoprotein-based assays should be employed as an adjunct to cystoscopy in the initial phases of hematuria triage and risk-adjusted surveillance programs, contingent upon the execution of prospective multicenter validation using predefined diagnostic thresholds, along with a regulatory assessment and health-economic analysis.