Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers
Year: 2018
Type: article
Abstract: 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.
Source: Life Science Alliance
Institutions: Westlake University, ETH Zurich, Institute for Molecular Systems Biology, University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, The University of Sydney, Children's Medical Research Institute, University Hospital Zurich, Kantonsspital St. Gallen, University of Zurich, University Hospital Frankfurt
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,500
OpenAlex ID: W2787358084