RT Journal Article
SR Electronic
T1 Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800042
DO 10.26508/lsa.201800042
VO 1
IS 2
A1 Tiannan Guo
A1 Li Li
A1 Qing Zhong
A1 Niels J Rupp
A1 Konstantina Charmpi
A1 Christine E Wong
A1 Ulrich Wagner
A1 Jan H Rueschoff
A1 Wolfram Jochum
A1 Christian Daniel Fankhauser
A1 Karim Saba
A1 Cedric Poyet
A1 Peter J Wild
A1 Ruedi Aebersold
A1 Andreas Beyer
YR 2018
UL https://www.life-science-alliance.org/content/1/2/e201800042.abstract
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.