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Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers


Guo, Tiannan; Li, Li; Zhong, Qing; Rupp, Niels J; Charmpi, Konstantina; Wong, Christine E; Wagner, Ulrich; Rueschoff, Jan H; Jochum, Wolfram; Fankhauser, Christian Daniel; Saba, Karim; Poyet, Cedric; Wild, Peter J; Aebersold, Ruedi; Beyer, Andreas (2018). Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers. Life Science Alliance, 1(2):e201800042.

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 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.

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 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.

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Contributors:Life Science Alliance, 2575-1077
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Urological Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2018
Deposited On:19 Jun 2018 12:17
Last Modified:20 Jun 2018 12:40
Publisher:Life Science Alliance
ISSN:2575-1077
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.26508/lsa.201800042

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