RT Journal Article
SR Electronic
T1 Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 250167
DO 10.1101/250167
A1 Tiannan Guo
A1 Li Li
A1 Qing Zhong
A1 Niels J Rupp
A1 Konstantina Charmpi
A1 Christie E Wong
A1 Ulrich Wagner
A1 Jan H Rueschoff
A1 Wolfram Jochum
A1 Christian Fankhauser
A1 Karim Saba
A1 Cedric Poyet
A1 Peter J Wild
A1 Ruedi Aebersold
A1 Andreas Beyer
YR 2018
UL http://biorxiv.org/content/early/2018/01/18/250167.abstract
AB Many tumors are characterized by large genomic heterogeneity and it remains unclear to what extent this impacts on protein biomarker discovery. Here, we quantified proteome intra-tissue heterogeneity (ITH) based on a multi-region analysis of 30 biopsy-scale prostate tissues using pressure cycling technology and SWATH mass spectrometry. We quantified 8,248 proteins and analyzed the ITH of 3,700 proteins. The level of ITH varied significantly depending on proteins and tissue types. Benign tissues exhibited generally more complex ITH patterns than malignant tissues. Spatial variability of ten prostate biomarkers was further 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 by quantifying spatial proteome variation and it demonstrates the feasibility by exploiting recent technological progress.