PMID- 29363612 OWN - NLM STAT- MEDLINE VI - 17 IP - 4 TI - Spatial Tissue Proteomics Quantifies Inter- and Intratumor Heterogeneity in Hepatocellular Carcinoma (HCC). PG - 810-825 CI - © 2018 by The American Society for Biochemistry and Molecular Biology, Inc. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell Proteomics JT - Molecular & cellular proteomics : MCP JID - 101125647 IS - 1535-9484 (Electronic) LID - 10.1074/mcp.RA117.000189 [doi] FAU - Buczak, Katarzyna AU - Buczak K AD - From the ‡European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany. FAU - Ori, Alessandro AU - Ori A AD - From the ‡European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany. AD - §Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany. FAU - Kirkpatrick, Joanna M AU - Kirkpatrick JM AD - §Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany. AD - ¶European Molecular Biology Laboratory, Proteomics Core Facility, Heidelberg, Germany. FAU - Holzer, Kerstin AU - Holzer K AD - ‖Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. FAU - Dauch, Daniel AU - Dauch D AD - **Department of Internal Medicine VIII, University Hospital Tübingen, 72076 Tübingen, Germany. AD - ‡‡Department of Physiology I, Institute of Physiology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany. FAU - Roessler, Stephanie AU - Roessler S AD - ‖Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. FAU - Endris, Volker AU - Endris V AD - ‖Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. FAU - Lasitschka, Felix AU - Lasitschka F AD - ‖Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. FAU - Parca, Luca AU - Parca L AD - From the ‡European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany. FAU - Schmidt, Alexander AU - Schmidt A AD - ¶¶Biozentrum, University of Basel, Basel, Switzerland. FAU - Zender, Lars AU - Zender L AD - **Department of Internal Medicine VIII, University Hospital Tübingen, 72076 Tübingen, Germany. AD - ‡‡Department of Physiology I, Institute of Physiology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany. AD - §§Translational Gastrointestinal Oncology Group, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. FAU - Schirmacher, Peter AU - Schirmacher P AD - ‖Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. FAU - Krijgsveld, Jeroen AU - Krijgsveld J AD - ¶European Molecular Biology Laboratory, Proteomics Core Facility, Heidelberg, Germany. AD - ‖‖European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany. AD - German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Singer, Stephan AU - Singer S AD - From the ‡European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany; martin.beck@embl.de stephan.singer@uni-greifswald.de. AD - ‖Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. FAU - Beck, Martin AU - Beck M AD - From the ‡European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany; martin.beck@embl.de stephan.singer@uni-greifswald.de. AD - European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, Heidelberg, Germany. IS - 1535-9476 (Linking) RN - 0 (Neoplasm Proteins) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Animals MH - Carcinoma, Hepatocellular/*metabolism MH - Female MH - Humans MH - Liver/metabolism MH - Liver Neoplasms/*metabolism MH - Male MH - Mass Spectrometry MH - Mice MH - Middle Aged MH - Neoplasm Proteins/*metabolism MH - Proteomics PMC - PMC5880102 DCOM- 20190213 LR - 20210217 DP - 201804 DEP - 20180123 AB - 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.