'On the Spot' Digital Pathology of Breast Cancer Based on Single-Cell Mass Spectrometry Imaging

Eva Cuypers*, Britt S R Claes, Rianne Biemans, Natasja G Lieuwes, Kristine Glunde, Ludwig Dubois, Ron M A Heeren

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The molecular pathology of breast cancer is challenging due to the complex heterogeneity of cellular subtypes. The ability to directly identify and visualize cell subtype distribution at the single-cell level within a tissue section enables precise and rapid diagnosis and prognosis. Here, we applied mass spectrometry imaging (MSI) to acquire and visualize the molecular profiles at the single-cell and subcellular levels of 14 different breast cancer cell lines. We built a molecular library of genetically well-characterized cell lines. Multistep processing, including deep learning, resulted in a breast cancer subtype, the cancer's hormone status, and a genotypic recognition model based on metabolic phenotypes with cross-validation rates of up to 97%. Moreover, we applied our single-cell-based recognition models to complex tissue samples, identifying cell subtypes in tissue context within seconds during measurement. These data demonstrate "on the spot" digital pathology at the single-cell level using MSI, and they provide a framework for fast and accurate high spatial resolution diagnostics and prognostics.

Original languageEnglish
Pages (from-to)6180-6190
Number of pages11
JournalAnalytical Chemistry
Volume94
Issue number16
Early online date12 Apr 2022
DOIs
Publication statusPublished - 26 Apr 2022

Keywords

  • HER2 STATUS
  • NEOADJUVANT CHEMOTHERAPY

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