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Peer-reviewedCC BYAnalytical chemistry

Integrating UHPLC-MS and MALDI-MSI for Spatial Nucleoside Profiling in FFPE Breast Cancer: A Multimodal Molecular Pathology Framework.

  • Jierong Wu1
  • Sabrina Geisberger1,2
  • Guido Mastrobuoni1,2
  • Kamil Lisek3
  • Sandra Raimundo3
  • Grit Nebrich4,5
  • Marta Grzeski4
  • Nikolaus Rajewsky3,6,7,8,9,10
  • Frederick Klauschen11
  • Oliver Klein4,5
  • Stefan Kempa1,2
11 affiliations
  1. 1Integrative Proteomics and Metabolomics, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin13125, Germany.
  2. 2MDC-Bruker Center of Excellence for Single Cell OMICS, Berlin10115, Germany.
  3. 3Systems 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.
  4. 4BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité─Universitätsmedizin Berlin, Berlin13353, Germany.
  5. 5Imaging Mass Spectrometry Unit, Berlin Institute of Health at Charité─Universitätsmedizin Berlin, Berlin13353, Germany.
  6. 6Charité─Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin10117, Germany.
  7. 7NeuroCure Cluster of Excellence, Charité─Universitätsmedizin Berlin, Berlin10117, Germany.
  8. 8German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin10117, Germany.
  9. 9German Cancer Consortium (DKTK), Heidelberg69120, Germany.
  10. 10National Center for Tumor Diseases (NCT), Partner Site Berlin, Berlin10117, Germany.
  11. 11Institute of Pathology, Ludwig Maximilians University Hospital Munich, Munich80336, Germany.
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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.

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Cite

BibTeXRIS
BibTeX
@article{wu2026integrating,
  title = {{Integrating UHPLC-MS and MALDI-MSI for Spatial Nucleoside Profiling in FFPE Breast Cancer: A Multimodal Molecular Pathology Framework.}},
  author = {Jierong Wu and Sabrina Geisberger and Guido Mastrobuoni and Kamil Lisek and Sandra Raimundo and Grit Nebrich and Marta Grzeski and Nikolaus Rajewsky and Frederick Klauschen and Oliver Klein and Stefan Kempa},
  journal = {Analytical chemistry},
  year = {2026},
  month = sep,
  doi = {10.1021/acs.analchem.6c00978},
  url = {https://europepmc.org/article/MED/42916394},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Integrating UHPLC-MS and MALDI-MSI for Spatial Nucleoside Profiling in FFPE Breast Cancer: A Multimodal Molecular Pathology Framework.
AU  - Jierong Wu
AU  - Sabrina Geisberger
AU  - Guido Mastrobuoni
AU  - Kamil Lisek
AU  - Sandra Raimundo
AU  - Grit Nebrich
AU  - Marta Grzeski
AU  - Nikolaus Rajewsky
AU  - Frederick Klauschen
AU  - Oliver Klein
AU  - Stefan Kempa
PY  - 2026
DA  - 2026/09/01
JO  - Analytical chemistry
DO  - 10.1021/acs.analchem.6c00978
UR  - https://europepmc.org/article/MED/42916394
AB  - 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.
SN  - 0003-2700
SN  - 1520-6882
ER  -