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dc.contributor.author
Sajic, Tatjana
dc.contributor.author
Ciuffa, Rodolfo
dc.contributor.author
Lemos, Vera
dc.contributor.author
Xu, Pan
dc.contributor.author
Leone, Valentina
dc.contributor.author
Chen, Li
dc.contributor.author
Williams, Evan G.
dc.contributor.author
Makris, Georgios
dc.contributor.author
Banaei Esfahani, Amir
dc.contributor.author
Heikenwalder, Mathias
dc.contributor.author
Schoonjans, Kristina
dc.contributor.author
Aebersold, Ruedi
dc.date.accessioned
2019-05-24T14:21:10Z
dc.date.available
2019-05-16T17:41:18Z
dc.date.available
2019-05-24T14:21:10Z
dc.date.issued
2019
dc.identifier.issn
2045-2322
dc.identifier.other
10.1038/s41598-019-43091-z
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/342578
dc.identifier.doi
10.3929/ethz-b-000342578
dc.description.abstract
To-date, most proteomic studies aimed at discovering tissue-based cancer biomarkers have compared the quantity of selected proteins between case and control groups. However, proteins generally function in association with other proteins to form modules localized in particular subcellular compartments in specialized cell types and tissues. Sub-cellular mislocalization of proteins has in fact been detected as a key feature in a variety of cancer cells. Here, we describe a strategy for tissue-biomarker detection based on a mitochondrial fold enrichment (mtFE) score, which is sensitive to protein abundance changes as well as changes in subcellular distribution between mitochondria and cytosol. The mtFE score integrates protein abundance data from total cellular lysates and mitochondria-enriched fractions, and provides novel information for the classification of cancer samples that is not necessarily apparent from conventional abundance measurements alone. We apply this new strategy to a panel of wild-type and mutant mice with a liver-specific gene deletion of Liver receptor homolog 1 (Lrh-1hep−/−), with both lines containing control individuals as well as individuals with liver cancer induced by diethylnitrosamine (DEN). Lrh-1 gene deletion attenuates cancer cell metabolism in hepatocytes through mitochondrial glutamine processing. We show that proteome changes based on mtFE scores outperform protein abundance measurements in discriminating DEN-induced liver cancer from healthy liver tissue, and are uniquely robust against genetic perturbation. We validate the capacity of selected proteins with informative mtFE scores to indicate hepatic malignant changes in two independent mouse models of hepatocellular carcinoma (HCC), thus demonstrating the robustness of this new approach to biomarker research. Overall, the method provides a novel, sensitive approach to cancer biomarker discovery that considers contextual information of tested proteins.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
A new class of protein biomarkers based on subcellular distribution: application to a mouse liver cancer model
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2019-05-06
ethz.journal.title
Scientific Reports
ethz.journal.volume
9
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Sci Rep
ethz.pages.start
6913
en_US
ethz.size
20 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
MitoModules: Biomarkers in context
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03663 - Aebersold, Rudolf (emeritus) / Aebersold, Rudolf (emeritus)
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03663 - Aebersold, Rudolf (emeritus) / Aebersold, Rudolf (emeritus)
ethz.grant.agreementno
166435
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Projekte Lebenswissenschaften
ethz.date.deposited
2019-05-16T17:41:23Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-05-24T14:21:42Z
ethz.rosetta.lastUpdated
2022-03-28T22:58:53Z
ethz.rosetta.versionExported
true
ethz.COinS
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