Publication
Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers
Journal Paper/Review - May 29, 2018
Guo Tiannan, Aebersold Ruedi, Wild Peter J, Poyet Cédric, Saba Karim, Fankhauser Christian Daniel, Jochum Wolfram, Rueschoff Jan H, Wagner Ulrich, Wong Christine E, Charmpi Konstantina, Rupp Niels J, Zhong Qing, Li Li, Beyer Andreas
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Brief description/objective
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.