Proteomics in bone malignancies: from bulk profiling to single-cell and ultra-low-input technologies

Area of Science:

• Oncology
• Proteomics
• Biochemistry

Background:

• Bone malignancies, especially high-grade sarcomas, present significant clinical challenges due to early spread and limited treatment options.
• Genomics and transcriptomics offer insights but do not fully capture the functional mechanisms driving tumor invasion, immune evasion, and therapy resistance.
• Proteomics and phosphoproteomics provide a complementary view of protein abundance and pathway activity, revealing actionable targets at the execution level.

Purpose of the Study:

• To synthesize recent advances in mass spectrometry-based proteomics for bone malignancies.
• To use osteosarcoma as a primary example for mature cohort-scale proteomics studies.
• To highlight the potential of proteomics in refining molecular subtyping and biomarker discovery for precision medicine in bone cancers.

Main Methods:

• Review of mass spectrometry-based proteomics studies, including bulk tissue, circulating proteomics, and extracellular vesicle/secretome profiling.
• Integration of proteomics data with genomics and transcriptomics for a multi-omics approach.
• Comparison of various proteomics workflows and discussion of barriers to clinical implementation.

Main Results:

• Proteomics data reveal recurrent biological axes in bone malignancies, including extracellular matrix remodeling, metabolic rewiring, and immune/stromal interactions.
• Multi-omics integration refines molecular subtyping and links bulk signatures to functional dependencies.
• Proteomics supports biomarker prioritization for translational applications, such as secretome-informed circulating candidates.

Conclusions:

• Emerging single-cell and ultra-low-input proteomics technologies offer new avenues for bone tumor research and clinical implementation.
• Proteomics is poised to become a key pillar in precision medicine for bone malignancies by connecting molecular alterations to functional states.
• Successful translation requires standardized protocols, multicenter validation, and development of targeted assays that demonstrate clinical utility.