Multi-region Proteome Analysis Quantifies Spatial Heterogeneity of Prostate Tissue Biomarkers

Overview

Journal Life Sci Alliance

Specialties Biochemistry
Biology
Cell Biology
Molecular Biology

Date 2018 Aug 10

PMID 30090875

Citations 26

Authors

Tiannan Guo

Li Li

Qing Zhong

Niels J Rupp

Konstantina Charmpi

Christine E Wong

Ulrich Wagner

Jan H Rueschoff

Wolfram Jochum

Christian Daniel Fankhauser

Karim Saba

Cedric Poyet

Peter J Wild

Ruedi Aebersold

Andreas Beyer

Affiliations

Soon will be listed here.

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.

Citing Articles

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