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Updated: Feb 12, 2026

Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
Proteomic analysis defines kinase taxonomies specific for subtypes of breast cancer
Kyla A L Collins1, Timothy J Stuhlmiller2,3, Jon S Zawistowski2,3
1Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Abstract:
Multiplexed small molecule inhibitors covalently bound to Sepharose beads (MIBs) were used to capture functional kinases in luminal, HER2-enriched and triple negative (basal-like and claudin-low) breast cancer cell lines and tumors. Kinase MIB-binding profiles at baseline without perturbation proteomically distinguished the four breast cancer subtypes. Understudied kinases, whose disease associations and pharmacology are generally unexplored, were highly represented in MIB-binding taxonomies and are integrated into signaling subnetworks with kinases that have been previously well characterized in breast cancer. Computationally it was possible to define subtypes using profiles of less than 50 of the more than 300 kinases bound to MIBs that included understudied as well as metabolic and lipid kinases. Furthermore, analysis of MIB-binding profiles established potential functional annotations for these understudied kinases. Thus, comprehensive MIBs-based capture of kinases provides a unique proteomics-based method for integration of poorly characterized kinases of the understudied kinome into functional subnetworks in breast cancer cells and tumors that is not possible using genomic strategies. The MIB-binding profiles readily defined subtype-selective differential adaptive kinome reprogramming in response to targeted kinase inhibition, demonstrating how MIB profiles can be used in determining dynamic kinome changes that result in subtype selective phenotypic state changes.
Insights
Multiplexed small molecule inhibitors bound to beads (MIBs) proteomically distinguished breast cancer subtypes. This method integrates understudied kinases into signaling networks, aiding subtype classification and understanding adaptive changes.
Area of Science:
- Proteomics
- Cancer Biology
- Biochemistry
Background:
- Breast cancer comprises distinct subtypes with varying clinical outcomes.
- Kinase signaling pathways are crucial in cancer development and progression.
- Many kinases remain understudied, limiting therapeutic strategies.
Purpose of the Study:
- To develop a proteomics-based method for profiling functional kinases across breast cancer subtypes.
- To integrate understudied kinases into functional signaling networks.
- To investigate adaptive kinome reprogramming in response to targeted inhibition.
Main Methods:
- Utilized multiplexed small molecule inhibitors covalently bound to Sepharose beads (MIBs) to capture kinases.
- Analyzed MIB-binding profiles from luminal, HER2-enriched, and triple-negative breast cancer cell lines and tumors.
- Employed computational analysis to define subtypes using kinase profiles.
Main Results:
- MIB-binding profiles proteomically distinguished the four breast cancer subtypes at baseline.
- Understudied kinases were identified and integrated into signaling subnetworks with well-characterized kinases.
- Subtypes could be defined using profiles of fewer than 50 kinases, including understudied, metabolic, and lipid kinases.
- MIB profiles revealed subtype-selective adaptive kinome reprogramming upon targeted kinase inhibition.
Conclusions:
- MIBs provide a unique proteomics approach to integrate understudied kinases into functional subnetworks for breast cancer.
- MIB-binding profiles can define subtypes and reveal dynamic kinome changes driving phenotypic state alterations.
- This method offers a powerful tool for understanding kinase function and developing targeted therapies in diverse breast cancer subtypes.
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