Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers.
- Guo T Department of Biology, Institute of Molecular Systems Biology, ETH, Zurich, Switzerland.
- Li L CECAD, University of Cologne, Cologne, Germany.
- Zhong Q Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
- Rupp NJ Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
- Charmpi K CECAD, University of Cologne, Cologne, Germany.
- Wong CE Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
- Wagner U Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
- Rueschoff JH Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
- Jochum W Institute of Pathology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
- Fankhauser CD Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Saba K Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Poyet C Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Wild PJ Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
- Aebersold R Department of Biology, Institute of Molecular Systems Biology, ETH, Zurich, Switzerland.
- Beyer A CECAD, University of Cologne, Cologne, Germany.
- 2018-08-10
Published in:
- Life science alliance. - 2018
English
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.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.26508/lsa.201800042
- PMID 30090875
- Persistent URL
- https://sonar.ch/global/documents/155317
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