Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers
Creators
- 1. Department of Biology, Institute of Molecular Systems Biology, ETH, Zurich, Switzerland
- 2. CECAD, University of Cologne, Cologne, Germany
- 3. Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; Cancer Data Science Group, ProCan, Children's Medical Research Institute, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia
- 4. Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
- 5. Institute of Pathology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
- 6. Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
- 7. Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt am Main, Germany
- 8. Department of Biology, Institute of Molecular Systems Biology, ETH, Zurich, Switzerland; Faculty of Science, University of Zurich, Zurich, Switzerland
- 9. CECAD, University of Cologne, Cologne, Germany;Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
Description
It remains unclear to what extent tumor heterogeneity impacts on protein biomarker discovery.
Here, we quantified proteome intra-tissue heterogeneity (ITH) based on a multi-region analysis of prostate tissues using pressure cycling technology and SWATH mass spectrometry. We quantified 6,873 proteins and analyzed the ITH of 3,700 proteins. The level of ITH varied depending on proteins and tissue types. Benign tissues exhibited more complex ITH patterns than malignant tissues. Spatial variability of ten prostate biomarkers was validated by immunohistochemistry in an independent cohort (n=83) using tissue microarrays. PSA was preferentially variable in benign prostatic hyperplasia, while GDF15 substantially varied in prostate adenocarcinomas. Further, we found that DNA repair pathways exhibited a high degree of variability in tumorous tissues, which may contribute to the genetic heterogeneity of tumors. This study conceptually adds a new perspective to protein biomarker discovery: it suggests that recent technological progress should be exploited to quantify and account for spatial proteome variation to complement biomarker identification and utilization.
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