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Updated: Jul 9, 2025
Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer
Christina Plattner1, Giorgia Lamberti1, Peter Blattmann2
1Biocenter, Institute of Bioinformatics, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Abstract:
Precision oncology approaches for patients with colorectal cancer (CRC) continue to lag behind other solid cancers. Functional precision oncology-a strategy that is based on perturbing primary tumor cells from cancer patients-could provide a road forward to personalize treatment. We extend this paradigm to measuring proteome activity landscapes by acquiring quantitative phosphoproteomic data from patient-derived organoids (PDOs). We show that kinase inhibitors induce inhibitor- and patient-specific off-target effects and pathway crosstalk. Reconstruction of the kinase networks revealed that the signaling rewiring is modestly affected by mutations. We show non-genetic heterogeneity of the PDOs and upregulation of stemness and differentiation genes by kinase inhibitors. Using imaging mass-cytometry-based profiling of the primary tumors, we characterize the tumor microenvironment (TME) and determine spatial heterocellular crosstalk and tumor-immune cell interactions. Collectively, we provide a framework for inferring tumor cell intrinsic signaling and external signaling from the TME to inform precision (immuno-) oncology in CRC.
Insights
Functional precision oncology using patient-derived organoids advances colorectal cancer (CRC) treatment. Phosphoproteomics reveals kinase inhibitor effects and tumor microenvironment interactions for personalized precision oncology strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Precision oncology for colorectal cancer (CRC) lags behind other solid tumors.
- Functional precision oncology offers a personalized treatment strategy by perturbing primary tumor cells.
- Measuring proteome activity landscapes is crucial for understanding treatment responses.
Purpose of the Study:
- To apply functional precision oncology to colorectal cancer using patient-derived organoids (PDOs).
- To analyze proteome activity landscapes via quantitative phosphoproteomics.
- To characterize the tumor microenvironment (TME) and its role in colorectal cancer signaling.
Main Methods:
- Quantitative phosphoproteomics on patient-derived organoids (PDOs).
- Kinase inhibitor perturbation assays.
- Imaging mass cytometry for tumor microenvironment (TME) profiling.
Main Results:
- Kinase inhibitors showed patient-specific off-target effects and pathway crosstalk.
- Signaling rewiring was minimally impacted by mutations, highlighting non-genetic heterogeneity.
- Kinase inhibitors modulated stemness and differentiation genes in PDOs.
- Tumor microenvironment (TME) profiling revealed spatial crosstalk and tumor-immune cell interactions.
Conclusions:
- A framework for inferring intrinsic tumor signaling and TME-derived external signaling was established.
- This approach can inform precision and immuno-oncology strategies for colorectal cancer (CRC).
- Functional precision oncology with phosphoproteomics and TME analysis enhances personalized CRC treatment.
