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Published on: June 6, 2020
Global proteome analysis of the NCI-60 cell line panel
Amin Moghaddas Gholami1, Hannes Hahne, Zhixiang Wu
1Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising, Germany. amin@tum.de.
Abstract:
The NCI-60 cell line collection is a very widely used panel for the study of cellular mechanisms of cancer in general and in vitro drug action in particular. It is a model system for the tissue types and genetic diversity of human cancers and has been extensively molecularly characterized. Here, we present a quantitative proteome and kinome profile of the NCI-60 panel covering, in total, 10,350 proteins (including 375 protein kinases) and including a core cancer proteome of 5,578 proteins that were consistently quantified across all tissue types. Bioinformatic analysis revealed strong cell line clusters according to tissue type and disclosed hundreds of differentially regulated proteins representing potential biomarkers for numerous tumor properties. Integration with public transcriptome data showed considerable similarity between mRNA and protein expression. Modeling of proteome and drug-response profiles for 108 FDA-approved drugs identified known and potential protein markers for drug sensitivity and resistance. To enable community access to this unique resource, we incorporated it into a public database for comparative and integrative analysis (http://wzw.tum.de/proteomics/nci60).
Insights
This study provides a comprehensive proteome and kinome profile of the NCI-60 cancer cell lines, identifying potential biomarkers for tumor properties and drug response. The data is now publicly accessible for further cancer research.
Area of Science:
- Proteomics and Cancer Biology
- Molecular Oncology
- Systems Biology
Background:
- The NCI-60 cell line panel is a crucial model for cancer research and drug discovery.
- Existing molecular characterization of NCI-60 is extensive but lacks a comprehensive quantitative proteome and kinome profile.
Purpose of the Study:
- To generate a quantitative proteome and kinome profile of the NCI-60 cell line panel.
- To identify potential protein biomarkers for tumor properties and drug sensitivity/resistance.
- To create a publicly accessible database for this data.
Main Methods:
- Quantitative mass spectrometry-based proteomics and kinomics.
- Bioinformatic analysis of proteome data, including clustering and differential expression analysis.
- Integration with public transcriptome data and drug-response profiles for 108 FDA-approved drugs.
Main Results:
- A quantitative proteome and kinome profile of 10,350 proteins (375 kinases) was generated for the NCI-60 panel.
- Bioinformatic analysis revealed tissue-specific clustering and identified hundreds of differentially regulated proteins as potential biomarkers.
- Integration with drug-response data identified protein markers for drug sensitivity and resistance.
- High similarity was observed between mRNA and protein expression levels.
Conclusions:
- The NCI-60 proteome and kinome dataset provides a valuable resource for cancer research.
- Identified protein biomarkers can advance understanding of tumor heterogeneity and drug response.
- The public database facilitates comparative and integrative analyses for the research community.
