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| Item Type: | Article |
|---|---|
| Title: | Integrating UHPLC-MS and MALDI-MSI for spatial nucleoside profiling in FFPE breast cancer: a multimodal molecular pathology framework |
| Creators: |
Wu, Jierong  ORCID: https://orcid.org/0000-0002-2413-0411, Geisberger, Sabrina ORCID: https://orcid.org/0000-0001-6477-1312, Mastrobuoni, Guido ORCID: https://orcid.org/0000-0003-4509-1295, Lisek, Kamil ORCID: https://orcid.org/0000-0002-2406-8830, Raimundo, Sandra ORCID: https://orcid.org/0009-0000-3353-5456, Nebrich, Grit, Grzeski, Marta, Rajewsky, Nikolaus ORCID: https://orcid.org/0000-0002-4785-4332, Klauschen, Frederick, Klein, Oliver and Kempa, Stefan ORCID: https://orcid.org/0000-0002-0696-9299
|
| 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. |
| Keywords: | Animals, Mice |
| Source: | Analytical Chemistry |
| ISSN: | 0003-2700 |
| Publisher: | American Chemical Society |
| Date: | 17 September 2026 |
| Official Publication: | https://doi.org/10.1021/acs.analchem.6c00978 |
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