Urinary Biomarkers in Bladder Cancer: Where Do We Stand and Potential Role of Extracellular Vesicles

Abstract

Extracellular vesicles (EVs) are small membrane vesicles released by all cells and involved in intercellular communication. Importantly, EVs cargo includes nucleic acids, lipids, and proteins constantly transferred between different cell types, contributing to autocrine and paracrine signaling. In recent years, they have been shown to play vital roles, not only in normal biological functions, but also in pathological conditions, such as cancer. In the multistep process of cancer progression, EVs act at different levels, from stimulation of neoplastic transformation, proliferation, promotion of angiogenesis, migration, invasion, and formation of metastatic niches in distant organs, to immune escape and therapy resistance. Moreover, as products of their parental cells, reflecting their genetic signatures and phenotypes, EVs hold great promise as diagnostic and prognostic biomarkers. Importantly, their potential to overcome the current limitations or the present diagnostic procedures has created interest in bladder cancer (BCa). Indeed, cystoscopy is an invasive and costly technique, whereas cytology has poor sensitivity for early staged and low-grade disease. Several urine-based biomarkers for BCa were found to overcome these limitations. Here, we review their potential advantages and downfalls. In addition, recent literature on the potential of EVs to improve BCa management was reviewed and discussed.

Extracellular Vesicles as Biomarkers Carriers in Bladder Cancer: Diagnosis, Surveillance, and Treatment

“…Nevertheless, despite their higher sensitivity comparing to cytology, they are not adequately sensitive in order to eliminate the need for cystoscopy. In addition, similarly to cytology, they lack sensitivity for low grade BCs and the positive predictive value can be adversely affected by the presence of hematuria, calculi, benign genitourinary disease, and inflammation [ 11 ].…”

Non‐Proteasomal Urine Activity in Bladder Cancer

“…The most important clinical needs in the treatment of bladder cancer is to establish panels of biomarkers of disease aggressiveness. Currently, cystoscopy, often supported by urine cytology, is called a ‘gold standard’ for diagnosis, and monitoring of bladder cancer [5] . However, cystoscopy is an invasive, painful, and expensive procedure which is not free of complications.…”

Pathogenesis and Diagnosis of Genitourinary Cancer

“…These comprehensive innovative analyses have led to new molecular classification based on the genomic expression profiles and the discovery of potential diagnostic and therapeutic molecular targets. The current special series includes 11 articles by international leading researchers who are involved in the investigation of several challenging issues, particularly novel potential biomarkers in GU cancers, using a variety of innovative approaches [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

“…In addition, Ide et al reviewed the role of steroid hormone receptors, such as androgen receptor, estrogen receptor-α, estrogen receptor-β, glucocorticoid receptor, progesterone receptor, and vitamin D receptor, in urothelial tumorigenesis [ 11 ]. De Oliveira et al updated the status of urinary biomarkers in the diagnosis and follow-up of bladder cancer, highlighting the emerging potential role of urinary EVs in BC diagnosis and management [ 13 ].…”