PT - JOURNAL ARTICLE AU - Tiannan Guo AU - Li Li AU - Qing Zhong AU - Niels J Rupp AU - Konstantina Charmpi AU - Christine E Wong AU - Ulrich Wagner AU - Jan H Rueschoff AU - Wolfram Jochum AU - Christian Daniel Fankhauser AU - Karim Saba AU - Cedric Poyet AU - Peter J Wild AU - Ruedi Aebersold AU - Andreas Beyer TI - Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers AID - 10.26508/lsa.201800042 DP - 2018 May 01 TA - Life Science Alliance PG - e201800042 VI - 1 IP - 2 4099 - https://www.life-science-alliance.org/content/1/2/e201800042.short 4100 - https://www.life-science-alliance.org/content/1/2/e201800042.full SO - Life Sci. Alliance2018 May 01; 1 AB - 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 Sequential Windowed Acquisition of all THeoretical fragment ion 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 10 prostate biomarkers was validated by immunohistochemistry in an independent cohort (n = 83) using tissue microarrays. Prostate-specific antigen was preferentially variable in benign prostatic hyperplasia, whereas growth/differentiation factor 15 substantially varied in prostate adenocarcinomas. Furthermore, 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.