{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, Hospital Universitari Sant Joan, 43204 Reus, Spain",
    "Unitat de Diagnòstic Molecular, Hospital Universitari Sant Joan, 43204 Reus, Spain",
    "Department of Basic Medical Sciences, Faculty of Medicine, Universitat Rovira I Virgili, 43204 Reus, Spain",
    "Unitat de Recerca Biomèdica, Institut de Recerca Biomèdica de la Catalunya Sud, 43204 Reus, Spain",
    "Institut d’Oncologia de la Catalunya Sud, 43204 Reus, Spain",
    "Grup d’Investigació Oncològica, Translacional, Epidemiològica i Clínica, Institut de Recerca Biomèdica de la Catalunya Sud, 43204 Reus, Spain",
    "Department of Medicine and Surgery, Faculty of Medicine, Universitat Rovira I Virgili, 43204 Reus, Spain"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Marc Andreu-Inglés",
      "orcid": "0009-0009-4476-2422"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Alina-Iuliana Onoiu",
      "orcid": "0009-0006-9483-498X"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "Marc Grifoll-Escoda",
      "orcid": "0000-0002-1948-328X"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Anna Hernández-Aguilera",
      "orcid": "0000-0003-0954-295X"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "Josep Gumà-Padró",
      "orcid": "0000-0001-7541-9832"
    },
    {
      "affs": [
        0,
        1,
        2,
        5
      ],
      "name": "Francesc Riu"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Karla Peña"
    },
    {
      "affs": [
        3,
        6
      ],
      "name": "Jordi Camps",
      "orcid": "0000-0002-3165-3640"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        5
      ],
      "name": "David Parada",
      "orcid": "0000-0002-8894-2312"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/465de9vxregzb.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198934",
  "fulltext_url": "https://europepmc.org/articles/PMC13665559",
  "id": "465de9vxregzb",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/19/8934",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2746|Bladder and Urothelial Cancer Treatments"
    ]
  ],
  "openalex": "W7221182069",
  "pdf_url": "https://europepmc.org/articles/PMC13665559?pdf=render",
  "pmcid": "PMC13665559",
  "pmid": "42884175",
  "published": "2026-10-08",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/465de9vxregzb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27198934",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/19/8934"
    },
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42884175",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42884175"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Bladder and Urothelial Cancer Treatments",
      "subfield": "surgery"
    }
  ],
  "title": "Urinary DNA Methylation Profiling Identifies a Biologically Distinct Subgroup of Low-Grade Urothelial Carcinoma with High-Grade-Associated Features",
  "title_text": "Urinary DNA Methylation Profiling Identifies a Biologically Distinct Subgroup of Low-Grade Urothelial Carcinoma with High-Grade-Associated Features",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/465de9vxregzb",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}