Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach

Area of Science:

• Biochemistry
• Proteomics
• Molecular Diagnostics

Background:

• Characterizing complex biological systems requires simultaneous measurement of millions of proteins, isoforms, and complexes.
• Existing technologies face limitations in achieving system-wide, native biomolecule coverage.

Purpose of the Study:

• To introduce Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT), a novel approach for comprehensive biomolecular profiling.
• To demonstrate ADAPT's utility in distinguishing breast cancer patients from healthy individuals using circulating exosomes.

Main Methods:

• Enrichment of a large library of single-stranded oligodeoxynucleotides (ssODNs) for exosome-associated molecules from patient and control samples.
• ssODN-mediated affinity purification coupled with mass spectrometry to identify low-abundance exosome-associated proteins and complexes.
• Sequencing of recovered ssODNs to generate quantitative measures for multi-analyte signature development and patient classification.

Main Results:

• ADAPT achieved unprecedented coverage of system-wide, native biomolecules.
• Identification of low-abundance exosome-associated proteins and complexes relevant to homeostasis and disease.
• Development of highly accurate multi-analyte signatures for patient classification, achieving an AUC of 0.73 when comparing healthy donors with biopsy-positive patients.

Conclusions:

• ADAPT is a powerful tool for high-resolution profiling of complex biological samples.
• The ADAPT approach enables accurate, non-invasive breast cancer detection through exosome analysis.
• This technology holds significant potential for advancing diagnostics and understanding of complex diseases.