{
  "abstract": "Formalin-fixed, paraffin-embedded (FFPE) tissues constitute the primary material for diagnostic pathology and retrospective clinical research, yet their use in metabolomics remains limited due to molecular cross-linking and analyte degradation. Here, we establish a cost-efficient molecular pathology workflow that integrates ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to quantify and spatially map nucleosides in FFPE breast cancer tissues. Optimized extraction using methanol yielded nucleoside profiles comparable to fresh-frozen tissues, while MALDI-MSI enabled the spatial visualization of nine nucleosides across distinct histological regions. Several nucleosides including deoxyadenosine and 5-formylcytosine showed strong discriminatory power between tumor stages, revealing progressive metabolic rewiring during breast cancer progression. Finally, spatial nucleoside patterns observed in a murine model were recapitulated in patient-derived FFPE tissues, underscoring the translational potential of nucleoside-based spatial metabolomics for clinical research and biomarker discovery. Together, this workflow establishes MALDI-MSI as a powerful and scalable spatial molecular pathology tool for interrogating nucleoside biology in archival breast cancer samples. Following MALDI-MSI, the same FFPE tissue sections can undergo laser capture microdissection, enabling genomic, proteomic, or targeted metabolomic profiling of MSI-defined tumor niches and microenvironmental regions. This integration directly links spatial nucleoside signatures to molecular alterations relevant to precision oncology in future.",
  "abstract_shown": true,
  "affiliations": [
    "Integrative Proteomics and Metabolomics, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin13125, Germany.",
    "MDC-Bruker Center of Excellence for Single Cell OMICS, Berlin10115, Germany.",
    "Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin13125, Germany.",
    "BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité─Universitätsmedizin Berlin, Berlin13353, Germany.",
    "Imaging Mass Spectrometry Unit, Berlin Institute of Health at Charité─Universitätsmedizin Berlin, Berlin13353, Germany.",
    "Charité─Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin10117, Germany.",
    "NeuroCure Cluster of Excellence, Charité─Universitätsmedizin Berlin, Berlin10117, Germany.",
    "German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin10117, Germany.",
    "German Cancer Consortium (DKTK), Heidelberg69120, Germany.",
    "National Center for Tumor Diseases (NCT), Partner Site Berlin, Berlin10117, Germany.",
    "Institute of Pathology, Ludwig Maximilians University Hospital Munich, Munich80336, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jierong Wu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sabrina Geisberger"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Guido Mastrobuoni"
    },
    {
      "affs": [
        2
      ],
      "name": "Kamil Lisek"
    },
    {
      "affs": [
        2
      ],
      "name": "Sandra Raimundo"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Grit Nebrich"
    },
    {
      "affs": [
        3
      ],
      "name": "Marta Grzeski"
    },
    {
      "affs": [
        2,
        5,
        6,
        7,
        8,
        9
      ],
      "name": "Nikolaus Rajewsky"
    },
    {
      "affs": [
        10
      ],
      "name": "Frederick Klauschen"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Oliver Klein"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Stefan Kempa",
      "orcid": "0000-0002-0696-9299"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f3t3yap17zkbk.bib",
  "cited_by": 0,
  "doi": "10.1021/acs.analchem.6c00978",
  "fulltext_url": "https://europepmc.org/articles/PMC13629170",
  "id": "f3t3yap17zkbk",
  "issns": [
    "0003-2700",
    "1520-6882"
  ],
  "landing_url": "https://europepmc.org/article/MED/42916394",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1607|Mass Spectrometry Techniques and Applications"
    ]
  ],
  "openalex": "W7213523787",
  "pdf_url": "https://europepmc.org/articles/PMC13629170?pdf=render",
  "pmcid": "PMC13629170",
  "pmid": "42916394",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f3t3yap17zkbk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42916394",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42916394"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1607|Mass Spectrometry Techniques and Applications",
      "subfield": "physical"
    }
  ],
  "title": "Integrating UHPLC-MS and MALDI-MSI for Spatial Nucleoside Profiling in FFPE Breast Cancer: A Multimodal Molecular Pathology Framework.",
  "title_text": "Integrating UHPLC-MS and MALDI-MSI for Spatial Nucleoside Profiling in FFPE Breast Cancer: A Multimodal Molecular Pathology Framework.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/f3t3yap17zkbk",
  "venue": "Analytical chemistry",
  "versions": []
}