Tumor-derived microRNAs as early predictive biomarkers for toxicity induced by immunotherapy in urothelial cancer.
14 affiliations
- 1Centro Universitario HM Hospitales de Ciencias de la Salud (CUHMED), Instituto de Investigación Sanitaria HM Hospitales, Universidad Camilo José Cela, Madrid, Spain.
- 2Human Genetic Variability Group, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid-Getafe University Hospital-Universidad Europea de Madrid), Madrid, Spain.
- 3Department of Medicine, Faculty of Medicine, Health and Sports, Universidad Europea de Madrid, Madrid, Spain.
- 4Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.
- 5Department of Medical Oncology, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
- 6Department of Pathological Anatomy, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
- 7Department of Pathological Anatomy, Hospital Universitario de Getafe, Madrid, Spain.
- 8Department of Medical Oncology, Hospital Universitario de Getafe, Madrid, Spain.
- 9Department of Pathological Anatomy, Hospital Universitario de Móstoles, Madrid, Spain.
- 10Department of Medical Oncology, Hospital Universitario de Móstoles, Madrid, Spain.
- 11Department of Medical Oncology, Hospital Universitario de Fuenlabrada, Madrid, Spain.
- 12Department of Pathological Anatomy, Hospital Universitario de Fuenlabrada, Madrid, Spain.
- 13Human Genetic Variability Group, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid-Getafe University Hospital-Universidad Europea de Madrid), Madrid, Spain. [email protected].
- 14Department of Cell Biology and Histology, Faculty of Medicine, Complutense University, Madrid, Spain. [email protected].
Abstract
Purpose
Immune checkpoint inhibitors (ICIs) have revolutionized advanced urothelial carcinoma (UC) treatment, yet efficacy is limited by immune-related adverse events (irAEs) necessitating treatment termination. Identifying biomarkers to predict irAE susceptibility is a critical unmet need for patient management. This exploratory study sought to identify tumor microRNA (miRNA) expression signatures associated with irAE risk in UC patients treated with ICIs.Methods
We analyzed a retrospective cohort of 108 UC patients treated with ICI therapy (PD-1 and PD-L1 blockade). Baseline tumor miRNA expression was quantified via RT-qPCR. Statistical analysis was performed to identify associations between baseline miRNA expression levels and the subsequent development of specific irAEs.Results
The irAE prevalence was high, affecting approximately one-third of the cohort. Low baseline tumor expression of miR-34c-5p and miR-493-5p was significantly associated with an increased risk of developing pneumonitis (p = 0.037) and asthenia (p = 0.027). Furthermore, borderline associations were observed for miR-146a-5p (hepatitis), miR-222-3p (pneumonitis) and miR-641 (anemia), supporting their roles in regulating immune homeostasis.Conclusion
In this exploratory study, tumor miRNA expression profiles, particularly the low baseline expression of miR-34c-5p and miR-493-5p, suggest a possible relationship with higher risk of developing toxicity during ICI treatments. Although further studies are needed to validate the utility of tumor miRNAs expression as biomarkers of ICI-induced toxicity, these preliminary results remark their possible utility as biomarkers in the clinical management of adverse effects from ICI treatment in UC patients.
Related
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- Immune and Circulating Biomarkers in Hepatocellular Carcinoma: Prognostic and Predictive Relevance for Immunotherapy
- Circulating and tumor microenvironment immunomarkers associate with immunotherapy efficacy in advanced bladder urothelial carcinoma: an exploratory multicenter study integrating genomic and immunophenotypic profiling
BibTeX
@article{gaibar2026tumorderived,
title = {{Tumor-derived microRNAs as early predictive biomarkers for toxicity induced by immunotherapy in urothelial cancer.}},
author = {Maria Gaibar and Alicia Romero-Lorca and Jose María Rodríguez-Piñas and Margarita Rubio and José Manuel Pérez-Ortiz and Diego Malón and Susana Hernando and Isabel Alemany and Francisca Inmaculada Camacho and Mercedes Cavanagh and Patricia Gómez and David Marrupe and Ana Manuela Martín and Radia Khedaoui and Ana Fernández-Santander and Apolonia Novillo},
journal = {Journal of cancer research and clinical oncology},
year = {2026},
month = aug,
doi = {10.1007/s00432-026-06582-x},
url = {https://europepmc.org/article/MED/43009659},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Tumor-derived microRNAs as early predictive biomarkers for toxicity induced by immunotherapy in urothelial cancer.
AU - Maria Gaibar
AU - Alicia Romero-Lorca
AU - Jose María Rodríguez-Piñas
AU - Margarita Rubio
AU - José Manuel Pérez-Ortiz
AU - Diego Malón
AU - Susana Hernando
AU - Isabel Alemany
AU - Francisca Inmaculada Camacho
AU - Mercedes Cavanagh
AU - Patricia Gómez
AU - David Marrupe
AU - Ana Manuela Martín
AU - Radia Khedaoui
AU - Ana Fernández-Santander
AU - Apolonia Novillo
PY - 2026
DA - 2026/08/11
JO - Journal of cancer research and clinical oncology
DO - 10.1007/s00432-026-06582-x
UR - https://europepmc.org/article/MED/43009659
AB - Purpose Immune checkpoint inhibitors (ICIs) have revolutionized advanced urothelial carcinoma (UC) treatment, yet efficacy is limited by immune-related adverse events (irAEs) necessitating treatment termination. Identifying biomarkers to predict irAE susceptibility is a critical unmet need for patient management. This exploratory study sought to identify tumor microRNA (miRNA) expression signatures associated with irAE risk in UC patients treated with ICIs.Methods We analyzed a retrospective cohort of 108 UC patients treated with ICI therapy (PD-1 and PD-L1 blockade). Baseline tumor miRNA expression was quantified via RT-qPCR. Statistical analysis was performed to identify associations between baseline miRNA expression levels and the subsequent development of specific irAEs.Results The irAE prevalence was high, affecting approximately one-third of the cohort. Low baseline tumor expression of miR-34c-5p and miR-493-5p was significantly associated with an increased risk of developing pneumonitis (p = 0.037) and asthenia (p = 0.027). Furthermore, borderline associations were observed for miR-146a-5p (hepatitis), miR-222-3p (pneumonitis) and miR-641 (anemia), supporting their roles in regulating immune homeostasis.Conclusion In this exploratory study, tumor miRNA expression profiles, particularly the low baseline expression of miR-34c-5p and miR-493-5p, suggest a possible relationship with higher risk of developing toxicity during ICI treatments. Although further studies are needed to validate the utility of tumor miRNAs expression as biomarkers of ICI-induced toxicity, these preliminary results remark their possible utility as biomarkers in the clinical management of adverse effects from ICI treatment in UC patients.
SN - 0171-5216
SN - 1432-1335
ER -