Clinical Utility of lncRNAs in Urothelial Carcinoma of the Bladder: Diagnostics, Risk Stratification, and Treatment Guidance
5 affiliations
- 1Faculty of Medicine, University of Rzeszów, Rejtana 16C, 35-959 Rzeszow, Poland
- 2Department of Nephrocardiology, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland
- 3Nikolay Pirogov Specialized Hospital in Lodz, Wolczanska, 90-531 Lodz, Poland
- 4Laboratory for Translational Research in Medicine, Centre for Innovative Research in Medical and Natural Sciences, University of Rzeszów, 35-959 Rzeszow, Poland
- 5Department of Human Immunology, Faculty of Medicine, College of Medical Sciences, University of Rzeszów, 35-959 Rzeszow, Poland
Abstract
Urothelial carcinoma of the bladder remains challenging to assess in real time. Standard tools such as white-light cystoscopy and urine cytology are essential, but both have recognized limitations, particularly for carcinoma in situ, low-grade disease and repeated long-term surveillance in non-muscle-invasive bladder cancer (NMIBC). Conventional risk models also show imperfect performance in contemporary practice, contributing to both overtreatment and delayed escalation in biologically aggressive disease. Long non-coding RNAs (lncRNAs) are emerging as attractive biomarkers because of their context-specific expression, measurable expression in tumor tissue and detectability in urine and blood, including within extracellular vesicles (EVs), such as exosomes that protect RNA from degradation. The potential clinical role of lncRNAs is determined by the specimen, molecular compartment, disease setting, and intended use. Urinary cell-free and urinary EV-associated lncRNAs currently have the strongest translational evidence for hematuria triage diagnostic support, recurrence-risk assessment, and longitudinal molecular monitoring. Tissue lncRNAs are most relevant to biological classification and prognostic refinement after transurethral resection or cystectomy, whereas blood-based lncRNAs may provide complementary information on systemic disease burden and treatment-associated response, particularly in muscle-invasive or advanced disease. Although several urinary multi-lncRNA panels have functioned as stand-alone statistical classifiers in development cohorts, no lncRNA assay has been prospectively validated to replace cystoscopy, cytology, histopathology, or established treatment-selection biomarkers in routine care. Repeatedly studied candidates include UCA1 and several exosomal/uEV-associated lncRNAs (e.g., TERC, SNHG16), while multi-lncRNA panels and combined strategies (including integration with established urine tests such as NMP22) may stabilize performance across biological and pre-analytical variability. Evidence also supports the concept of longitudinal “molecular response” monitoring using liquid-based lncRNA readouts, although truly predictive, treatment-interaction evidence remains limited. Across studies, performance is strongly influenced by the urine compartment analyzed (pellet/sediment, cell-free urine, or urinary EVs (uEVs)/exosomes) and by pre-analytical handling and normalization choices. lncRNA assays are unlikely to replace cystoscopy in the near term, but they have clear potential as decision-support tests that complement clinical risk assessment, cytology, and other urine-based platforms. This work synthesizes mechanistic and clinically annotated evidence on lncRNAs in bladder cancer, with an emphasis on urine-based and uEV/exosomal assays. The search strategy covered publications from 1 January 2015 to 30 December 2025, with emphasis on most recent clinically relevant studies, and included mechanistic studies with functional validation, liquid biopsy/urine studies, and evidence syntheses.
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BibTeX
@article{lawinski2026clinical,
title = {{Clinical Utility of lncRNAs in Urothelial Carcinoma of the Bladder: Diagnostics, Risk Stratification, and Treatment Guidance}},
author = {Janusz Ławiński and Beata Franczyk and Abdusalam Sagr and Karolina Popek and Jacek Tabarkiewicz},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219461},
url = {https://www.mdpi.com/1422-0067/27/21/9461},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical Utility of lncRNAs in Urothelial Carcinoma of the Bladder: Diagnostics, Risk Stratification, and Treatment Guidance
AU - Janusz Ławiński
AU - Beata Franczyk
AU - Abdusalam Sagr
AU - Karolina Popek
AU - Jacek Tabarkiewicz
PY - 2026
DA - 2026/10/23
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219461
UR - https://www.mdpi.com/1422-0067/27/21/9461
AB - Urothelial carcinoma of the bladder remains challenging to assess in real time. Standard tools such as white-light cystoscopy and urine cytology are essential, but both have recognized limitations, particularly for carcinoma in situ, low-grade disease and repeated long-term surveillance in non-muscle-invasive bladder cancer (NMIBC). Conventional risk models also show imperfect performance in contemporary practice, contributing to both overtreatment and delayed escalation in biologically aggressive disease. Long non-coding RNAs (lncRNAs) are emerging as attractive biomarkers because of their context-specific expression, measurable expression in tumor tissue and detectability in urine and blood, including within extracellular vesicles (EVs), such as exosomes that protect RNA from degradation. The potential clinical role of lncRNAs is determined by the specimen, molecular compartment, disease setting, and intended use. Urinary cell-free and urinary EV-associated lncRNAs currently have the strongest translational evidence for hematuria triage diagnostic support, recurrence-risk assessment, and longitudinal molecular monitoring. Tissue lncRNAs are most relevant to biological classification and prognostic refinement after transurethral resection or cystectomy, whereas blood-based lncRNAs may provide complementary information on systemic disease burden and treatment-associated response, particularly in muscle-invasive or advanced disease. Although several urinary multi-lncRNA panels have functioned as stand-alone statistical classifiers in development cohorts, no lncRNA assay has been prospectively validated to replace cystoscopy, cytology, histopathology, or established treatment-selection biomarkers in routine care. Repeatedly studied candidates include UCA1 and several exosomal/uEV-associated lncRNAs (e.g., TERC, SNHG16), while multi-lncRNA panels and combined strategies (including integration with established urine tests such as NMP22) may stabilize performance across biological and pre-analytical variability. Evidence also supports the concept of longitudinal “molecular response” monitoring using liquid-based lncRNA readouts, although truly predictive, treatment-interaction evidence remains limited. Across studies, performance is strongly influenced by the urine compartment analyzed (pellet/sediment, cell-free urine, or urinary EVs (uEVs)/exosomes) and by pre-analytical handling and normalization choices. lncRNA assays are unlikely to replace cystoscopy in the near term, but they have clear potential as decision-support tests that complement clinical risk assessment, cytology, and other urine-based platforms. This work synthesizes mechanistic and clinically annotated evidence on lncRNAs in bladder cancer, with an emphasis on urine-based and uEV/exosomal assays. The search strategy covered publications from 1 January 2015 to 30 December 2025, with emphasis on most recent clinically relevant studies, and included mechanistic studies with functional validation, liquid biopsy/urine studies, and evidence syntheses.
SN - 1422-0067
ER -