Comparative Shotgun Proteomics Reveals the Characteristic Protein Signature of Osteosarcoma Subtypes

Abstract

Osteosarcoma is a primary malignant bone tumor affecting adolescents and young adults. This study aimed to identify proteomic signatures that distinguish between different osteosarcoma subtypes, providing insights into their molecular heterogeneity and potential implications for personalized treatment approaches. Using advanced proteomic techniques, we analyzed FFPE tumor samples from a cohort of pediatric osteosarcoma patients representing four various subtypes. Differential expression analysis revealed a significant proteomic signature that discriminated between these subtypes, highlighting distinct molecular profiles associated with different tumor characteristics. In contrast, clinical determinants did not correlate with the proteome signature of pediatric osteosarcoma. The identified proteomics signature encompassed a diverse array of proteins involved in focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathways, and proteoglycans in cancer, among the top enriched pathways. These findings underscore the importance of considering the molecular heterogeneity of osteosarcoma during diagnosis or even when developing personalized treatment strategies. By identifying subtype-specific proteomics signatures, clinicians may be able to tailor therapy regimens to individual patients, optimizing treatment efficacy and minimizing adverse effects.

Proteomics in orthopedic research: Recent studies and their translational implications

“…28 OS is the most prevalent primary bone tumor that primarily affects adolescents. 29 Alaa 30 and colleagues set out to characterize the relationship between proteomic signatures of OS subtypes to demographic and clinical characteristics of patients. They studied OS tissue specimens from 33 patients.…”

“…34 By promoting DDX3-hnRNPK's proapoptotic function, it may prove to be a promising therapeutic target to induce apoptosis in OS. 30 For the chondroblastic subtype, tenascin C (TNC), Lumican (LUM), collagen type 12 A1 (COL12A1), collagen 6A3 (COL6A3), and biglycan (BGN) were unique differential proteins that characterized this group. LUM was found to be an endogenous inhibitor of TGF-β2 activity, which regulates OS adhesion.…”