Skip to content
DraconiticResearch
Search Sources API
182,460 studies31 sourcesUpdated just now
Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Urinary DNA Methylation Profiling Identifies a Biologically Distinct Subgroup of Low-Grade Urothelial Carcinoma with High-Grade-Associated Features

  • Marc Andreu-Inglés1,2,3,4
  • Alina-Iuliana Onoiu3,4
  • Marc Grifoll-Escoda5,6,7
  • Anna Hernández-Aguilera1,2,3,4
  • Josep Gumà-Padró5,6,7
  • Francesc Riu1,2,3,6
  • Karla Peña1,2,3,4
  • Jordi Camps4,7
  • David Parada1,2,3,4,6
7 affiliations
  1. 1Department of Pathology, Hospital Universitari Sant Joan, 43204 Reus, Spain
  2. 2Unitat de Diagnòstic Molecular, Hospital Universitari Sant Joan, 43204 Reus, Spain
  3. 3Department of Basic Medical Sciences, Faculty of Medicine, Universitat Rovira I Virgili, 43204 Reus, Spain
  4. 4Unitat de Recerca Biomèdica, Institut de Recerca Biomèdica de la Catalunya Sud, 43204 Reus, Spain
  5. 5Institut d’Oncologia de la Catalunya Sud, 43204 Reus, Spain
  6. 6Grup d’Investigació Oncològica, Translacional, Epidemiològica i Clínica, Institut de Recerca Biomèdica de la Catalunya Sud, 43204 Reus, Spain
  7. 7Department of Medicine and Surgery, Faculty of Medicine, Universitat Rovira I Virgili, 43204 Reus, Spain
Read full textPDFDOICite

Abstract

Bladder cancer surveillance remains challenging because conventional methods do not fully capture the biological heterogeneity within histologically low-grade urothelial carcinoma (LGUC). We evaluated whether urinary DNA methylation profiling using Bladder EpiCheck™ can identify clinically relevant LGUC subgroups in a retrospective single-center cohort of 134 patients with paired histopathology, urine cytology, and methylation results. Methylation positivity increased across negative histopathology, LGUC, and high-grade urothelial carcinoma (HGUC) (18.4%, 51.4%, and 91.5%, respectively). Within LGUC, 19 of 37 tumors (51.4%) were methylation-positive. Their EpiScores overlapped those of HGUC, whereas methylation-negative LGUCs exhibited scores similar to negative histopathology. Gaussian mixture modeling independently supported a bimodal distribution. Methylation-positive LGUCs demonstrated a higher Ki67 labeling index, more frequent MTAP loss (33.3% vs. 11.8%), and more recurrences, including recurrence as HGUC, than methylation-negative LGUCs. Conventional nuclear morphometry did not distinguish between the two LGUC subgroups. These exploratory findings suggest that urinary DNA methylation may identify a biologically distinct subset of histologically low-grade tumors with selected high-grade-associated features. Prospective external validation is required before methylation status can inform surveillance or treatment decisions.

Related

  1. Integrated Transcriptomic and Network Analysis Identifies Diagnostic and Immune-Associated Hub Genes in Urothelial Carcinoma
    Shaza N. Alkhatib, Ammena Y. Binsaleh, Nawal Al-Hoshani +3
    BiomedicinesPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  2. Blood DNA methylation profiling identifies candidate diabetic kidney disease risk signatures in the PROPHECY Aboriginal Diabetes Study
    Scott Maxwell, Ishant Khurana, Sam Buckberry +10
    Communications MedicinePeer-reviewedCC BY 4.0General medicineCrossref
  3. Single-cell profiling uncovers a rare mesenchymal-like urothelial state associated with sarcomatoid bladder cancer.
    Justine J Jacobi, Dongbo Xu, Kyle Wieczorek +9
    Cell death & diseasePeer-reviewedCC BYFull textOncologyEurope PMCPMC
  4. Genome-Wide DNA methylation profiling of tissue-plasma pairs identifies Novel cfDNA biomarkers for the diagnosis of gastric cancer
    Hailing Ou, Jinli Miao, Fusheng Ling +6
    PLOS GeneticsPeer-reviewedCC BYFull textMolecular biology & gene regulationGenetics & genomicsPLOSEurope PMC
  5. Cancer type-specific profiling of chromatin regulator mutations identifies recurrent and co-occurring gene sets associated with improved survival following immune checkpoint therapy
    D. Bukovec, M. Gjorgjievska, S. Kocevska +5
    medRxivPreprintAll rights reservedFull textOncologymedRxiv

Cite

BibTeXRIS
BibTeX
@article{andreuingles2026urinary,
  title = {{Urinary DNA Methylation Profiling Identifies a Biologically Distinct Subgroup of Low-Grade Urothelial Carcinoma with High-Grade-Associated Features}},
  author = {Marc Andreu-Inglés and Alina-Iuliana Onoiu and Marc Grifoll-Escoda and Anna Hernández-Aguilera and Josep Gumà-Padró and Francesc Riu and Karla Peña and Jordi Camps and David Parada},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27198934},
  url = {https://www.mdpi.com/1422-0067/27/19/8934},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Urinary DNA Methylation Profiling Identifies a Biologically Distinct Subgroup of Low-Grade Urothelial Carcinoma with High-Grade-Associated Features
AU  - Marc Andreu-Inglés
AU  - Alina-Iuliana Onoiu
AU  - Marc Grifoll-Escoda
AU  - Anna Hernández-Aguilera
AU  - Josep Gumà-Padró
AU  - Francesc Riu
AU  - Karla Peña
AU  - Jordi Camps
AU  - David Parada
PY  - 2026
DA  - 2026/10/08
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27198934
UR  - https://www.mdpi.com/1422-0067/27/19/8934
AB  - Bladder cancer surveillance remains challenging because conventional methods do not fully capture the biological heterogeneity within histologically low-grade urothelial carcinoma (LGUC). We evaluated whether urinary DNA methylation profiling using Bladder EpiCheck™ can identify clinically relevant LGUC subgroups in a retrospective single-center cohort of 134 patients with paired histopathology, urine cytology, and methylation results. Methylation positivity increased across negative histopathology, LGUC, and high-grade urothelial carcinoma (HGUC) (18.4%, 51.4%, and 91.5%, respectively). Within LGUC, 19 of 37 tumors (51.4%) were methylation-positive. Their EpiScores overlapped those of HGUC, whereas methylation-negative LGUCs exhibited scores similar to negative histopathology. Gaussian mixture modeling independently supported a bimodal distribution. Methylation-positive LGUCs demonstrated a higher Ki67 labeling index, more frequent MTAP loss (33.3% vs. 11.8%), and more recurrences, including recurrence as HGUC, than methylation-negative LGUCs. Conventional nuclear morphometry did not distinguish between the two LGUC subgroups. These exploratory findings suggest that urinary DNA methylation may identify a biologically distinct subset of histologically low-grade tumors with selected high-grade-associated features. Prospective external validation is required before methylation status can inform surveillance or treatment decisions.
SN  - 1422-0067
ER  -