Spatial tissue proteomics quantifies inter- and intratumor heterogeneity in hepatocellular carcinoma (HCC)

• Verfasst von: Buczak, Katarzyna [VerfasserIn]
• Verfasst von: Holzer, Kerstin [VerfasserIn]
• Verfasst von: Rössler, Stephanie [VerfasserIn]
• Verfasst von: Endris, Volker [VerfasserIn]
• Verfasst von: Lasitschka, Felix [VerfasserIn]
• Verfasst von: Schirmacher, Peter [VerfasserIn]
• Verfasst von: Krijgsveld, Jeroen [VerfasserIn]
• Verfasst von: Singer, Stephan [VerfasserIn]
• Titel: Spatial tissue proteomics quantifies inter- and intratumor heterogeneity in hepatocellular carcinoma (HCC)
• Verf.angabe: Katarzyna Buczak, Alessandro Ori, Joanna M. Kirkpatrick, Kerstin Holzer, Daniel Dauch, Stephanie Roessler, Volker Endris, Felix Lasitschka, Luca Parca, Alexander Schmidt, Lars Zender, Peter Schirmacher, Jeroen Krijgsveld, Stephan Singer, and Martin Beck
• E-Jahr: 2018
• Jahr: April 1, 2018
• Umfang: 16 S.
• Fussnoten: Gesehen am 22.10.2019
• Titel Quelle: Enthalten in: Molecular & cellular proteomics
• Ort Quelle: Bethesda, Md. : The American Society for Biochemistry and Molecular Biology, 2002
• Jahr Quelle: 2018
• Band/Heft Quelle: 17(2018), 4, Seite 810-825
• ISSN Quelle: 1535-9484
• DOI: doi:10.1074/mcp.RA117.000189
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1679337556

Abstract

The interpatient variability of tumor proteomes has been investigated on a large scale but many tumors display also intratumoral heterogeneity regarding morphological and genetic features. It remains largely unknown to what extent the local proteome of tumors intrinsically differs. Here, we used hepatocellular carcinoma as a model system to quantify both inter- and intratumor heterogeneity across human patient specimens with spatial resolution. We defined proteomic features that distinguish neoplastic from the directly adjacent nonneoplastic tissue, such as decreased abundance of NADH dehydrogenase complex I. We then demonstrated the existence of intratumoral variations in protein abundance that re-occur across different patient samples, and affect clinically relevant proteins, even in the absence of obvious morphological differences or genetic alterations. Our work demonstrates the suitability and the benefits of using mass spectrometry-based proteomics to analyze diagnostic tumor specimens with spatial resolution. Data are available via ProteomeXchange with identifier PXD007052.