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Updated: Dec 8, 2025
Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Integrating proteomics into precision oncology
Leonie W Wahjudi1, Stephan Bernhardt1, Khalid Abnaof1
1Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Abstract:
DNA sequencing and RNA sequencing are increasingly applied in precision oncology, where molecular tumor boards evaluate the actionability of genetic events in individual tumors to guide targeted treatment. To work toward an additional level of patient characterization, we assessed the abundance and activity of 27 proteins in 134 patients whose tumors had previously undergone whole-exome and RNA sequencing within the Molecularly Aided Stratification for Tumor Eradication Research (MASTER) program of National Center for Tumor Diseases, Heidelberg. Proteomic and phosphoproteomic targets were selected to reflect the most relevant therapeutic baskets in MASTER. Among six different therapeutic baskets, the proteomic data supported treatment recommendations that were based on DNA and RNA analyses in 10% to 57% and frequently suggested alternative treatment options. In several cases, protein activities explained the patients' clinical course and provided potential explanations for treatment failure. Our study indicates that the integrative analysis of DNA, RNA and protein data may refine therapeutic stratification of individual patients and, thus, holds potential to increase the success rate of precision cancer therapy. Prospective validation studies are needed to advance the integration of proteomic analysis into precision oncology.
Insights
Integrating DNA, RNA, and protein analysis in cancer improves patient stratification. This multi-omics approach refines precision cancer therapy by revealing protein activities that explain clinical outcomes and treatment responses.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Precision oncology utilizes DNA and RNA sequencing for targeted cancer treatment.
- Molecular tumor boards assess genetic alterations to guide therapy selection.
- There is a need for deeper patient characterization beyond genomic data.
Purpose of the Study:
- To assess the abundance and activity of 27 proteins in 134 cancer patients.
- To evaluate the utility of proteomic data in refining treatment recommendations within the MASTER program.
- To explore the integration of proteomic data with DNA and RNA sequencing for enhanced cancer therapy.
Main Methods:
- Proteomic and phosphoproteomic analysis of 27 targets in 134 tumor samples.
- Selection of targets based on relevant therapeutic baskets in the MASTER program.
- Integrative analysis of DNA, RNA, and protein data.
Main Results:
- Proteomic data supported DNA/RNA-based treatment recommendations in 10-57% of cases.
- Protein activities frequently suggested alternative therapeutic options.
- Protein activities correlated with patient clinical course and treatment failure.
Conclusions:
- Integrative analysis of multi-omics data (DNA, RNA, protein) can refine patient stratification in precision oncology.
- Proteomic profiling holds potential to increase the success rate of precision cancer therapy.
- Prospective validation studies are necessary to integrate proteomic analysis into routine clinical practice.
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