Benjamin Balluff (Presenter)
Authorship: Benjamin Balluff (1), Kristian Unger (2), Ron Heeren (1), Axel Walch (2), Liam A. McDonnell (3)
(1) Maastricht University, The Netherlands; (2) Helmholtz Zentrum Muenchen, Germany; (3) Leiden University Medical Center, The Netherlands
A so far unresolved factor influencing the evolution of cancer and the clinical course of patients is intra-tumor heterogeneity. In this presentation a pipeline using imaging mass spectrometry will be presented for the systematic de novo discovery of clinically detrimental tumor subpopulations. Therefore, spatially-resolved mass spectra are clustered for revealing molecularly distinct regions with the tumor. The simultaneous segmentation of many samples and investigation if the presence of certain clusters is statistically associated with the clinical outcome of the patients, allows identifying phenotypic tumor subpopulations which –after dissection– can be further molecularly characterized by other omics approaches.
Introduction: An essential and so far unresolved factor influencing the evolution of cancer and the clinical management of patients is intra-tumor clonal and phenotypic heterogeneity. Here we aim for the first systematic approach for the de novo discovery of clinically detrimental molecular tumor subpopulations.
Methods: Tumor-specific mass spectra were acquired using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry from tissues of 63 gastric carcinoma and 32 breast carcinoma patients. The mass spectra, representing the proteomic heterogeneity within tumor areas, were grouped by a corroborated statistical clustering algorithm in order to obtain segmentation maps of molecularly distinct regions. It was tested if these regions represent different phenotypic tumor subpopulations by linking their presence to the patients’ clinical data.
Results: In this proof-of-principle study, several of the detected tumor subpopulations showed to be associated with a different overall-survival of the gastric cancer patients (P=0.025) or the presence of loco-regional metastases in patients with breast cancer (P=0.036).
Conclusions: The procedure presented is generic and opens novel options in cancer research as it reveals microscopically indistinct tumor subpopulations that have an adverse impact on clinical outcome.
References & Acknowledgements:
IP Royalty: no
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